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.