Relationships between NADPH Content and Benzo(a)pyrene Metabolism in Normal and Glucose-6-Phosphate Dehydrogenase-Deficient Human Fibroblasts
Previous work in our laboratory has shown that human skin fibroblasts (HSF) and human lymphocytes carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) exhibit a great decrease in hexose monophosphate shunt and in NADP /NADPH ratio1,2. G6PD deficiency protects in vitro growing HSF and lymphocytes from benzo(a)pyrene (BaP) toxicity. G6PD-deficient HSF give rise in soft agar, after incubation with BaP, to a lower number of colonies than normal HSF1. Aryl hydrocarbon hydroxylase (AHH) activities are lower in G6PD-deficient cells, when tested in the absence of exogenous NADPH2. G6PD-deficient cells, incubated in vitro with BaP, produce low amounts of organic- and water-soluble BaP metabolites and show a decreased ability to form BaP-7,8-diol-9,10-epoxide and BaP-DNA adducts3,4.
KeywordsG6PD Deficiency Deficient Cell Polar Fraction Human Skin Fibroblast Mouse Embryo Fibroblast
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- 1.F. Feo, L. Pirisi, R. Pascale, L. Daino, S. Frassetto and R. Garcea, Modulatory effect of glucose-6-phosphate dehydrogenase deficiency on the benzo(a)pyrene toxicity and transforming activity for in vitro cultured human skin fibroblasts, Cancer Res. 38:3419 (1984).Google Scholar
- 2.F. Feo, L. Pirisi, R. Pascale, L. Daino, S. Frassetto, S. Zanetti and R. Garcea, Modulatory mechanisms of chemical carcinogenesis: the role of the NADPH pool in benzo(a)pyrene activation, Toxicol. Pathol. 12:262 (1984).Google Scholar
- 4.F. Feo, M. E. Ruggiu, L. Lenzerini, R. Garcea, L. Daino, S. Frassetto, V. Addis, L. Gaspa and R. Pascale, Benzo(a)pyrene metabolism by lymphocytes from normal individuals and individuals carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, Int. J. Cancer 39:560 (1987).PubMedCrossRefGoogle Scholar
- 7.L. A. Reinke, P. McManus, F. C. Kauffman and R. G. Thurman, Benzo(a)-pyrene phenol production by perfused rat liver and its inhibition by ethanol, Cancer Res. 4:1681 (1982).Google Scholar