The differential effects of the carcinogen dimethylnitrosamine on isocitrate and 6-phosphogluconate metabolism in single intact cells |
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Authors: | Elli Kohen Cahide Kohen Joseph G. Hirschberg Alain W. Wouters Bo Thorell |
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Affiliation: | 1. Papanicolaou Cancer Research Institute, Miami, FL U.S.A.;2. Department of Biology, University of Miami, Coral Gables, FL U.S.A.;3. Department of Physics, University of Miami, Coral Gables, FL U.S.A.;4. Department of Pathology, School of Medicine, University of Miami, Coral Gables, FL U.S.A.;5. Laboratory for Optics and Astrophysics, Department of Physics, University of Miami, Coral Gables, FL U.S.A.;6. Department of Pathology, Karolinska Institute, Stockholm Sweden |
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Abstract: | A microspectrofluorimetric study is made of the influence of dimethylnitrosamine on NADP reduction, following sequential microinjections into the same L cell, of two substrates: (1) isocitrate, with activity of isocitrate dehydrogenase both in the extramitochondrial and intramitochondrial compartments, (2) 6-phosphogluconate, with activity of the dehydrogenase in the extramitochondrial compartment. In control L cells a two-step reduction of NAD(P) is obtained followed by relatively slow reoxidation. In the minutes which follow addition of carcinogen, e.g., dimethylnitrosamine, to the cell medium the isocitrate and 6-phosphogluconate-induced transient NADP reoxidation is decreased in magnitude compared to control, while the rate constant of NADPH reoxidation is considerably accelerated, possibly due to requirements at the level of the microsomal metabolizing system. Observations within the first hour of carcinogen addition suggest an interesting system for evaluating the immediate actions of carcinogens at extranuclear sites: i.e., a comparative study of NADP reduction-reoxidation rate constants via injection of substrates for extra- vs. intramitochondrial pathways. |
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Keywords: | Dimethylnitrosamine Isocitrate 6-Phosphogluconate Intact cell Carcinogen |
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