Bioavailability of PCBs to Male Laboratory Rats Maintained on Litters of Contaminated Soils: PCB Burden and Induction of Alkoxyresorufin O-Dealkylase Activities in Liver and Lung

Male rats from the Sprague-Dawley laboratory strain were maintained in the laboratory during 3 days and 1 night on litters containing a reference soil and different amounts of a soil, mainly polluted by PCBs (207 ppm expressed in Aroclor? 1254; SIII soil). Two categories of biomarkers of exposure were measured in both liver and lung of these rats: PCB burdens and activities of microsomal liver and lung cytochrome P450–dependent mono-oxygenases, namely ethoxy-, pentoxy-, and benzoxy-resorufin O-dealkylase activities (EROD, PROD, and BROD, respectively). PCB burdens in liver and lung of rats exposed to SIII soil were 1,845 and 241 ppb, respectively (expressed in Aroclor? 1254 equivalents). EROD, PROD, and BROD were significantly induced in the liver of rats exposed to SIII soil, while only EROD activity was induced in the lung. Induction of hepatic EROD activity was ∼3- to 5.4-fold; pulmonary EROD activity was induced by 9- to 12-fold. In the lung, PROD and BROD activities were inhibited. When rats were exposed to SIII soil diluted with various amounts of standard ISO soil, a nearly linear dose-response relationship was found between the level of PCBs in the litter and EROD activity in both liver and lung. A nonlinear dose-response relationship exists with hepatic BROD activity; no dose-response relationship was observed with hepatic PROD and pulmonary PROD and BROD activities. EROD activity measurement in both liver and lung of rats maintained on a litter of PCB polluted soil was used to assess the bioavailability to mammals of PCBs. Received: 16 December 1996/Accepted: 18 November 1997     

Estrogenic effects of polychlorinated biphenyls and relation to cytochrome P4501A activity in the endangered goodeid fish Ameca splendens

The present study examines the relationships between cytochrome P4501A (CYP1A) activity and vitellogenin (VTG) induction in Ameca splendens elicited by a polychlorinated biphenyl (PCB) mixture. Ethoxyresorufin-O-deethylase (EROD) activity, mRNA levels of VTG, and VTG induction were evaluated in male and female fish exposed for 1, 2, 4, 8, and 16 d to a commercial PCB mixture. Polychlorinated biphenyls induced higher EROD in both sexes and this induction was higher in females than in males. Maximum EROD and VTG induction occurred on day 1 in females, while in males these maxima occurred on days 8 and 16. A correlation between EROD and VTG induction was found only in males (p<0.001), and VTG induction was also higher in males than in females (p<0.01). Exposure to PCBs elicited increases in VTG expression and induction over time in males, while in females these decreased at the end of the exposure period. Deficiencies in the feedback mechanisms of male A. splendens exposed in the wild to xenoestrogens such as PCBs have probably contributed to alter the sex ratio of wild populations of this species.     

In ovo exposure to polychlorinated biphenyls: reproductive effects on second-generation American kestrels

The reproductive success of wild birds has been affected by exposure to multiple contaminants. Reproduction of captive American kestrels (Falco sparverius) was suppressed when adult birds were exposed to dietary polychlorinated biphenyls (PCBs). In this study, the reproductive effects of in ovo exposure to PCBs is explored, along with determining effects on reproduction in second-generation birds indirectly exposed to PCBs. Reproductive changes in this subsequent generation are examined separately in male and female birds. Captive American kestrels (F. sparverius) were hatched from clutches with eggs containing environmentally relevant levels of total PCBs (34.0 μg/g whole egg WW versus 0 μg/g controls); parent birds had been fed PCB-spiked (Aroclor 1248:1254:1260) food (7 mg/kg BW day⁻¹) for 100 days until their eggs hatched. In 1999, the second-generation PCB birds were paired with unexposed kestrels having reproductive experience. In ovo PCB exposure suppressed egg laying completely in 25% of PCB females and resulted in delays in clutch initiation and smaller clutch sizes for PCB male and female pairs. There was no evidence in this study of in ovo PCB treatment effects on fertility or hatching success. The decline in reproductive success was also reflected in the reduced fledging success and higher incidence of complete brood mortality of PCB nestlings. Differences between in ovo–exposed PCB males and females but not between controls were evident in reproductive success. In ovo PCB exposure appears to have had greater effects on female kestrels until clutch completion, with a greater time lag between pairing and egg laying, reduced numbers of pairs laying eggs, and smaller clutches being laid. In ovo PCB exposure has greater effects later in the breeding season on male kestrels, which had poorer hatching and fledging success relative to the PCB females. Possible behavioral and physiological mechanisms involved in these reproductive changes are discussed. Received: 25 July 2000/Accepted: 8 December 2000     

Effects of polychlorinated biphenyls on liver ultrastructure, hepatic monooxygenases, and reproductive success in the barbel

Polychlorinated biphenyls (PCBs) are organochlorinated micropollutants ubiquitously distributed in the environment. They are known to be strong inducers of hepatic monooxygenases in fish. This can adversely affect reproduction by increasing steroid metabolism. In this work, adult barbels were contaminated with food containing Aroclor 1260, a commercial PCB mixture from Monsanto, at environmentally relevant concentrations. A significant increase in cytochrome P450 was observed, and two particularly sensitive enzymes, ethoxyresorufin o-deethylase (EROD) and ethoxycoumarin o-deethylase (ECOD), were strongly induced. Electron microscopy revealed alterations in liver ultrastructure in contaminated fish, principally an increase in the number of cisternae of the rough endoplasmic reticulum, drastic glycogen depletion, dissolution of mitochondrial contents, and appearance of myelin figures. Contamination was also studied in relation to reproductive success in a hatchery. Contaminated males displayed no alteration in milt quality, but PCBs did alter female reproductive parameters. Total mortality of eggs and larvae increased significantly with the level of PCBs in the eggs. The most highly contaminated fish did not even spawn. All the adverse effects recorded here tended to be reversible when the intoxication ended, sometimes after only a 1-year detoxication period.     

Blarina brevicauda as a biological monitor of polychlorinated biphenyls: evaluation of hepatic cytochrome P450 induction

We assessed the value of short-tailed shrews (Blarina brevicauda) as a possible biomonitor for polychlorinated biphenyl pollution through measurement of the induction of hepatic cytochrome P450 and associated enzyme activities. First, we checked the inducibility of four monooxygenases (benzyloxyresorufin-O-dealkylase [BROD], ethoxyresorufin-O-dealkylase [EROD], methoxyresorufin-O-dealkylase [MROD], and pentoxyresorufin-O-dealkylase [PROD]) by measuring the activity of these enzymes in hepatic microsomes prepared from shrews injected with beta-naphthoflavone (betaNF) or phenobarbital (PB), typical inducers of cytochrome P4501A (CYP1A) and CYP2B enzyme families, respectively. Enzyme activity was induced in shrews that received betaNF but not in shrews that received PB; PROD was not induced by either exposure. Later, shrews were exposed to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1242:1254, in 1:2 ratio) at 0.6, 9.6, and 150 ppm in food, for 31 d. Induction in these shrews was measured by specific enzyme activity (BROD, EROD, and MROD) in hepatic microsomes, by western blotting of solubilized microsomes against antibodies to CYP1A or CYP2B, and by duration of sodium pentobarbital-induced sleep. These three CYP enzymes were induced in shrews by PCBs at similar levels of exposure as in cotton rat (Sigmodon hispidus). Neither sleep time nor the amount of CYP2B family protein were affected by PCB exposure. Blarina brevicauda can be a useful biomonitor of PCBs that induce CYP1A, especially in habitats where they are the abundant small mammal.     

Cytological changes in association with ethoxyresorufin o-deethylase induction in fish upon dietary exposure to benzo[a]pyrene

Juvenile areolated grouper (Epinephelus areolatus) were exposed to two levels of dietary benzo[a]pyrene (BaP; 0.25-12.5 microg/g body wt/d) for four weeks, followed by four weeks of depuration. Significant increase in hepatic ethoxyresorufin O-deethylase (EROD) activities was found after one week, preceding an increase in lipopigments (as measured by quantitative transmission electron microscopy) in week 2 of exposure. The EROD activities in the BaP-treated fish subsided at week 4 of exposure and throughout the depuration period. Lipopigments in the high-dose group appeared to be more persistent than that of the EROD activity during the exposure period and remained significantly higher than that of the controls at week 4. Levels of lipopigments, however, rapidly subsided on withdrawal of BaP exposure. These results appear to suggest that changes in EROD activities would precede cytological changes and that both the observed cytological and biochemical changes are reversible. Results of the present study also lend further support to our earlier findings on Solea ovata, that a significant relationship exists between EROD activity and lipopigment accumulation (as measured by volume density, absolute volume, numerical density, and absolute density; r = 0.483-0.358, p < 0.05), regardless of fish species (S. ovata and aerolated grouper) as well as the routes of exposure to BaP (intraperitoneal injection or dietary exposure). This provides strong supporting evidence that elevated EROD activities in fish liver do not merely indicate exposure to polyaromatic hydrocarbons (PAHs) but are also associated with significant biological effects. Our results showed that hepatic EROD activity and lipopigments could be used to indicate recent exposure of the fish to BaP/PAHs.     

Tilapia Larvae Aroclor 1254 Exposure: Effects on Gonads and Circulating Thyroid Hormones During Adulthood

Aroclor 1254 a polychlorinated biphenyls (PCBs) mixture, when administrated through the diet, was previously found to inhibit adult tilapia (Oreochromis niloticus) reproduction. Since fish larvae can be more sensitive to contaminants, the objectives of this study were to evaluate in adults the impact in gonad development and in thyroid function of Aroclor 1254 administrated at larvae stages. Aroclor 1254 exposed tilapia presented both ovary and testicular alterations and a decline in T4 plasma concentration while T3 remained unaltered. This work shows exposure to Aroclor 1254 during tilapia early life stages causes a disruption of the reproductive axis that enables reproduction.     

Subacute and Reproductive Effects in Mink from Exposure to Fusarium fujikuroi Culture Material (M-1214) Containing Known Concentrations of Moniliformin

This study was conducted to ascertain the subacute and reproductive effects in mink (Mustela vison) resulting from exposure to moniliformin, a toxic mycotoxin produced by Fusarium fungi. In a preliminary trial, adult mink were presented diets that contained targeted concentrations of 10, 20, 40, 80, 160, or 240 ppm moniliformin provided by F. fujikuroi culture material (M-1214). The mink fed diets that contained more than 40 ppm moniliformin refused to eat significant quantities of feed. Feeding adult mink diets that contained 8.1 or 17.0 ppm (wet weight) moniliformin, provided by F. fujikuroi culture material, in a 30-day subacute trial produced no significant adverse effects on feed consumption, body weights, hematologic parameters, or serum chemical values, and notable histologic changes in tissues that were examined. In the reproduction trial, female mink were exposed to the same dietary concentrations of moniliformin provided by F. fujikuroi culture material as in the subacute test from 2 weeks prior to the breeding season until their offspring (kits) were 8 weeks old. Consumption of the high-dose (17 ppm) diet resulted in significant neonatal mortality and reduced kit body weights at birth and at 8 weeks of age. Necropsy of 8-week-old kits from the control and high-dose groups revealed no gross or histologic lesions or alterations in liver, lung, or heart tissues that could account for the mortality observed in the kits exposed to the culture material. These results indicate that long-term (105–135 days) dietary exposure to F. fujikuroi culture material containing 17 ppm moniliformin is not lethal to adult female mink, but can have adverse effects on neonatal mink. Received: 18 April 1997/Accepted: 7 April 1998     

Chronic toxicity of diethylenetriamine pentaacetic acid to crimson-spotted rainbowfish (Melanotaenia fluviatilis): effects on reproduction, condition, and ethoxyresorufin O-deethylase activity.

The chronic effects of the chelating agent diethylenetriamine pentaacetic acid (DTPA) on reproduction, condition factor, liver somatic index (LSI), gonad somatic index (GSI), and ethoxyresorufin O-deethylase (EROD) activity of adult Australian crimson-spotted rainbowfish (Melanotaenia fluviatilis) were assessed. Breeding groups of three females and two males were exposed to 0, 1, 10, or 100 mg/liter DTPA (nominal) in a 28-day "static-renewal" experiment. Overall, the toxicity of DTPA to adult crimson-spotted rainbowfish was relatively low. Reproduction was not affected at concentrations up to 100 mg/liter DTPA, although an early effect on hatchability was potentially attributed to direct toxicity to rainbowfish eggs. DTPA also had little effect on the condition of adult rainbowfish, with condition factor and GSI being unaffected at concentrations up to 100 mg/liter, the latter finding supporting the reproduction results. However, LSI in male rainbowfish exposed to 100 mg/liter was significantly lower than in those exposed to 1 mg/liter DTPA (P相似文献   

Activities of liver and lung cytochrome P450-dependent monooxygenases and antioxidant enzymes in laboratory and wild Norway rats exposed to reference and contaminated soils

Laboratory and wild Norway rats were exposed in the laboratory to an uncontaminated soil and to a soil from a site contaminated with petrochemical waste. Activities of microsomal lung and liver cytochrome P450-dependent monooxygenases, including 7-ethoxyresorufin O-deethylase (EROD), 7-pentoxyresorufin O-depentylase (PROD) and 7-benzoxyresorufin O-debenzylase (BROD) were measured at selected times during the course of the study. The highest degree of induction of hepatic EROD (7-fold) was shown after 3 days of exposure to the contaminated soil. However, two months later, the EROD activity declined to fourfold increase over the control. The PROD and BROD activities displayed a similar time course of induction, but the degree of induction was lower. The induction of hepatic monooxygenase activities was observed in both laboratory and wild rats. Lung monooxygenase EROD was highly induced (up to 28-fold) after 3 days of exposure, and the activity remained elevated throughout the two-month experiment. BROD and PROD activities were not induced. The activities of three antioxidant enzymes, namely superoxide dismutase, glutathione peroxidase (Se- and non-Se-dependent) and catalase also were measured in lung and liver cytosol, but no significant changes were observed after two months of exposure to contaminated soil.     

Subchronic toxicity and reproduction effects of tri-n-butyltin oxide in Japanese quail

A subchronic toxicity/reproduction study was performed in Japanese quails that were fed a diet containing 0, 24, 60, and 150 mg tri-n-butyltin oxide (TBTO) per kg basal diet for 6 weeks. Eggs produced during the 6 weeks of treatment were incubated and hatched, and chicks hatched from eggs collected in weeks 5 and 6 of exposure were reared for 2 weeks. In parent quail, neither diminished food consumption nor any overt toxic or histopathologic signs were observed following exposure to TBTO. A statistically significant decrease in hatchability and increase in percent of chicks found dead in the shell were observed following TBTO exposure at concentrations of 60 and 150 mg/kg food. However, no significant, adverse effects were recorded on total egg production, eggshell thickness and cracked eggs. Blood chemistry parameters of birds measured at the last day of TBTO treatment revealed a statistically significant decrease in serum aspartate aminotransferase (ASAT) enzyme activity among both sexes in all treatment groups. In addition, a statistically significant dose-related decrease in serum calcium level was observed in females only, while serum follicle stimulating hormone (FSH) levels were statistically significantly reduced in male birds in all treatment groups (approximately 50% of the controls).Moreover, a significant decrease in hepatic microsomal 7-ethoxyresorufin (EROD) activity was recorded in females fed 24 and 60 mg TBTO/kg diet and males fed 60 and 150 mg TBTO/kg diet, whereas pentoxyresorufin-o-deetylase (PROD) activity was only significantly decreased in males fed 150 mg TBTO/kg diet. No TBTO related effects were found on serum alanine aminotransferase (ALAT), serum total thyroxine (TT₄), luteinizing hormone (LH) or retinol levels in both sexes. In summary, TBTO affected mainly reproduction in Japanese quail at a dose where no overt toxicity is observed.     

阿特拉津对斑马鱼影响的研究

目的研究农药阿特拉津是否具有雌激素效应。方法选择斑马鱼为受试动物，随机分为对照组和阿特拉津暴露组。观察不同浓度的阿特拉津（0．1、0．5、1．0、5．0、10．0mg／L）对斑马鱼的生长、体内卵黄蛋白原（Vtg）含量及肝脏7-乙氧基-3-异吩口恶唑酮-脱乙基酶（EROD）酶活力的影响。结果经14d暴露后，阿特拉津浓度低于1．0mg/kg时雄性斑马鱼体重增长分别为对照组的1．57、1．81和2．07倍；当阿特拉津浓度高于1．0mg／kg时，实验组斑马鱼体重出现负增长现象。当阿特拉津浓度为1．0、5．0和10．0mg／kg时，实验组雌性斑马鱼体重分别为对照组的-0．42、-2．18和-1．32倍。阿特拉津可诱导雄性斑马鱼体内Vtg表达，具有雌激素效应并抑制肝脏中EROD酶活力，与对照组相比，差异均有统计学意义（P〈0．01）。结论阿特拉津对水生动物有明确的生长和生殖毒性。     

Joint effects of dietary cadmium and polychlorinated biphenyls on metallothionein induction, lipid peroxidation and histopathology in the kidneys and liver of bank voles

Free-living bank voles have been shown to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions. The present study was designed to find out whether polychlorinated biphenyls (PCBs), common environmental co-contaminants, increase susceptibility to Cd toxicity through inhibition of metallothionein (MT) synthesis-a low molecular weight protein that is considered to be a primary intracellular component of the protective mechanism. For 12 weeks, the male bank voles were provided with diets containing Cd (0.05 microg/g (control) and 10 microg/g dry wt) and PCBs (0, 10 and 50 microg/g dry wt) alone or in combination under long (16 h) and short (8 h) photoperiods. At the end of exposure period, histological examinations and analyses of MT, Cd, Fe and lipid peroxidation in the kidneys and liver were carried out. Dietary PCBs did not affect Cd inducibility of renal MT, but decreased it significantly in the liver; however, no signs of Cd toxicity (measured by histopathology) occurred in both organs. On the contrary, PCBs at the highest dose increased significantly lipid peroxidation in the kidneys and liver (4-fold) only in the bank voles raised under a long photoperiod; the PCB-induced hepatic lipid peroxidation was accompanied by extensive histopathological changes including hepatocyte enlargement, necrosis and steatosis. Co-treatment with dietary Cd significantly suppressed the increase in lipid peroxidation and apparently reduced hepatic damage. These data indicate that (1) dietary PCBs do not enhance Cd toxicity in the kidneys and liver of bank voles and (2) dietary Cd suppresses PCB-induced hepatotoxicity that appears to be photoperiod-dependent.     

Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.     

Comparative hepatic activity of xenobiotic-metabolizing enzymes and concentrations of organohalogens and their hydroxylated analogues in captive Greenland sledge dogs (Canis familiaris)

A captive study was performed with Greenland sledge dogs (Canis familiaris) fed a naturally organohalogen-contaminated diet (Greenland minke whale [Balaenoptera acutorostrata] blubber; exposed group) or a control diet (pork fat; control group). The catalytic activity of major xenobiotic-metabolizing phase I and II hepatic microsomal enzymes was assessed. Relative to control dogs, ethoxyresorufin-O-deethylase (EROD) activity in exposed dogs was twofold higher (p = 0.001). Testosterone hydroxylation yielded 6beta- and 16beta-hydroxy (OH) testosterone and androstenedione, with higher rates of production (23-27%; p < or = 0.03) in the exposed individuals. In the exposed dogs, epoxide hydrolase (EH) activity was 31% higher (p = 0.02) relative to the control dogs, whereas uridine diphosphoglucuronosyl transferase (UDPGT) activity was not different (p = 0.62). When the exposed and control dogs were combined, the summed (sigma) plasma concentrations of OH-polychlorinated biphenyl (PCB) congeners were predicted by plasma sigmaPCB concentrations and EROD activity (p < or = 0.04), whereas testosterone hydroxylase, EH, and UDPGT activities were not significant predictors of these concentrations. Consistent results were found for individual OH-PCB congeners and their theoretical precursor PCBs (e.g., 4-OH-CB-187 and CB-183, and 4-OH-CB-146 and CB-146) and for EROD activity. No association was found between sigmaOH-polybrominated diphenyl ether (PBDE) and sigmaPBDE plasma concentrations, or between potential precursor-metabolite pairs, and the enzyme activities. The present results suggest that liver microsomal EROD activity and plasma PCB concentrations have a greater (e.g., relative to EH activity) predictive power for the occurrence of plasma OH-PCB residues in sledge dogs. These results also suggest that plasma OH-PBDEs likely are not products of cytochrome P450-mediated transformation but, rather, are accumulated via the diet.     

Sublethal effects of esfenvalerate pulse-exposure on spawning and non-spawning Australian crimson-spotted rainbowfish (Melanotaenia fluviatilis)

The spawning activity of the Australian crimson-spotted rainbowfish (Melanotaenia fluviatilis) was monitored over a period of nine days. After the first three days, groups of rainbowfish were pulse-exposed with the pyrethroid insecticide esfenvalerate at one of six nominal concentrations (0, 1, 3.2, 10.0, 32.0, or 100 /L). The effects of esfenvalerate on fecundity, total hatch, hatchability of eggs, frequency of hatch defects, and the survival and growth of subsequent larvae were monitored. Hepatic cytochrome P-450 activity (ECOD, EROD, EFCOD) was measured six days post-exposure in controls and fish exposed to 32 g/L esfenvalerate. Cytochrome P-450 activity was also measured in single sex populations of male and female rainbowfish similarly exposed. The effects of esfenvalerate pulse-exposure on the lymphoproliferation of immune cells isolated from spawning and non-spawning groups of rainbowfish were examined in a second experiment.Over 75% of fish pulse-exposed to 100 g/L esfenvalerate died, and males in all treatments were more strongly affected than females. There was a negative correlation between pesticide concentration, fecundity, and total hatch. All eggs laid in the first three days post-exposure failed to hatch in some treatments, although esfenvalerate pulse-exposure did not increase the prevalence of deformed larvae. Esfenvalerate pulse-exposure significantly increased hepatic ECOD activity in male rainbowfish but had no effect on male EROD or EFCOD activities. There was no significant effect of esfenvalerate pulse-exposure on hepatic EROD, ECOD, or EFCOD activities of female rainbowfish. Unstimulated lymphocyte proliferation was lower in treated female rainbowfish than non-exposed female fish, and there was some evidence of an interaction with spawning activity.     

Evaluation of biomarkers of exposure and effect in juvenile areolated grouper (Epinephelus areolatus) on foodborne exposure to benzo[a]pyrene

Food-borne benzo[a]pyrene (B[a]P) was administered daily to juvenile grouper (Epinephelus areolatus) at two environmentally realistic concentrations (a low dose of 0.25 microg B[a]P/g body wt/d and a high dose of 12.5 microg B[a]P/g body wt/d) to investigate and relate temporal changes in body burden of B[a]P, hepatic ethoxyresorufin-O-deethylase (EROD) activities, growth, RNA:DNA ratio, estradiol, testosterone, and triiodothyronine (T3). After feeding with B[a]P diets for four weeks, fish were fed with normal diet for another four weeks to study recovery of the various biomarkers during the depuration period. After one week of exposure, both body muscle B[a]P burdens and hepatic EROD activities significantly increased. Body burdens were stable in tissues until the fourth week of exposure, when concentrations in the high-dose group increased markedly, at which time a concomitant decrease in EROD was found. During the depuration period, body burdens decreased in the second week, and EROD declined in the first week. Growth and RNA:DNA ratio were unaltered. Despite large variations found in sex steroid levels, elevation of testosterone was clearly evident in the fourth week, showing that B[a]P may disrupt the balance of sex steroids in fish. Significantly, increases in plasma-free T3 concentrations were found in the fourth week of exposure and the first week of depuration, suggesting that development and reproduction may potentially be at risk during chronic exposures. Our data also suggest that these hormonal disturbances are not persistent and that normal hormonal levels can be restored soon after contamination is abated.     

The Effect of Paraquat on Hepatic EROD Activity, Liver, and Gonadal Histology in Males and Females of Nile Tilapia, Oreochromis niloticus, Exposed at Different Temperatures

The activity of fish monooxygenases has been used as a monitoring tool to evaluate contamination by cytochrome P450 inducing agents. In this study ethoxyresorufin O-deethylase (EROD) activity was analyzed in males and females of Nile tilapia exposed to a low concentration of paraquat (PQ) at 17°C and 27°C. PQ-treated fish showed a high hepato-somatic index, except females acclimated at 17°C. No differences were found for the gonado-somatic index (GSI) between males. However, PQ-treated females showed high GSI values (6.46 ± 1.75) when compared with the control group (2.30 ± 0.26) maintained at 27°C. Males and females exposed to PQ showed higher microsomal protein values than the control group (9.46 ± 0.22 vs. 6.20 ± 0.18 at 17°C; 9.51 ± 0.35 vs. 4.70 ± 0.19 mg of protein at 27°C, in PQ-treated and control groups, respectively). The EROD activity was high in females exposed to PQ when compared with the control group at 17° and 27°C. The liver histology showed that PQ also caused some hepatic alterations of parenchyma, like vacuolization, necrosis, and an increase of macrophages aggregates and eosinophilic granular cells. Females exposed to PQ showed a greater increase of late-vitellogenic (22.2 ± 3.2) and mature (12.1 ± 2.0) percentage of oocytes than the control group (9.9 ± 3.0 and 8.0 ± 4.3, respectively), and a lower percentage of primary oocytes (8.0 ± 3.3) at 27°C. In short, this work has advanced new knowledge on the influence of gender in biotransformation activity and the reproductive activity of Nile tilapia exposed to a low concentration of paraquat, and demonstrated that their effects could be observed at different temperatures.     

Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec

Some polychlorinated biphenyl (PCB) congeners are CYP1A1 inducers, and induction of this enzyme in the placenta has been linked to adverse effects on fetal development. The objective of this study was to determine if the body burden of PCBs is related to placental CYP1A1 activity in Inuit women from Nunavik (northern Québec), a population highly exposed to organochlorines. Placenta and cord blood samples were obtained from 35 Inuit women and 30 women from a southern Québec community exposed to background levels of organochlorines. We measured PCB concentrations in all cord plasma samples and in a subset of placenta samples from the Nunavik group and assessed CYP1A1 activity (ethoxyresorufin-O-deethylase; EROD) in placental microsomes from all participants. Concentrations of PCBs in cord plasma were strongly correlated to those in placenta (Pearson's r) = 0.77-0.97, p < 0.001) and were on average 4-fold higher in Inuit women than in southern Québec women [for PCB 153, the geometric means (geometric SDs) were 83.3 (1.9) ng/g lipid vs. 16.9 (1.6) ng/g lipid, respectively]. Despite this difference in PCB body burden, both study groups had similar EROD activities when data were stratified according to tobacco smoking. Although simple correlation analysis first showed that placental EROD activity was correlated with PCB 153 plasma concentration in the Nunavik group, a multivariate analysis failed to demonstrate a significant contribution of PCBs to EROD activity when tobacco smoking was included in the analysis. We conclude that dietary exposure to PCBs in Inuit women from Nunavik does not significantly influence EROD activity in the placenta, implicating tobacco smoking as the major modulating factor.     

Low hepatic ethoxyresorufin-O-deethylase activity correlates with high organochlorine concentrations in Atlantic tomcod from the Canadian east coast

A suppression of hepatic ethoxyresorufin-O-deethylase (EROD) activity was reported recently in large-sized Atlantic tomcod (Microgadus tomcod) from the St. Lawrence Estuary (SLE; QC, Canada), possibly related to chronic exposure to persistent contaminants and/or to emaciation. In the present study, hepatic concentrations of organochlorine contaminants and biological responses were measured in female tomcods from three estuaries located on the Canadian east coast: The SLE, the Miramichi (ME), and the Richibucto (RE) Rivers Estuaries (NB, Canada). Tomcods from the SLE had higher hepatic concentrations of organochlorine contaminants than tomcods from the ME and RE. For example, concentrations of polychlorinated biphenyls (PCBs, lipid wt) were 2.5 to 4 times higher, and concentrations of mirex and chlordanes were 6 times higher, in tomcods from the SLE than in tomcods from the other sites. Concentrations of polycyclic aromatic hydrocarbons (PAHs) metabolites in the bile did not differ among sites. The pattern of biological responses differed markedly between the SLE and the two other sites. Tomcods from the SLE had 1.5 times higher concentrations of DNA adducts and 2 times higher rates of hepatocellular proliferation, but 20 times lower hepatic EROD activity, than tomcods from the ME and RE. Lipid content was not correlated with EROD activity, indicating that low hepatic lipid content alone does not cause suppression of EROD activity in Atlantic tomcod. In contrast, for the three sites combined, EROD activity decreased as concentrations of PCBs increased. Within sites, hepatic PCB concentrations increased as lipid content decreased. This study supports the hypothesis that low EROD activity in SLE tomcods is related to chronic exposure to organochlorine contaminants.