Benzo(a)pyrene metabolism by lymphocytes from normal individuals and individuals carrying the mediterranean variant of glucose-6-phosphate dehydrogenase

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Abstract
In vitro growing human lymphocytes (HL) and fibroblasts, isolated from glucose‐6‐phosphate dehydrogenase (G6PD)‐de‐ficient subjects (Mediterranean variant), show a sharp decrease in this enzymatic activity and in NADPH:NADP+ ratio. These cells are less able than controls to hydroxylate benzo(a)pyrene (BaP) when tested in the absence of an exogenous NADPH‐generating system. They exhibit great resistance to the toxic effect of BaP. G6PD‐deficient fibroblasts are less prone than controls to in vitro transformation by BaP. To investigate whether this depends on a decreased production of active BaP metabolites and BaP:DNA adducts by G6PD‐deficient cells, BaP metabolism was studied in G6PD‐deficient HL cultured in vitro in the presence of mitogens and treated with BaP for 24 hr. HPLC profiles of organo‐ and water‐soluble metabolites revealed that both types of benzo(a)anthracene (BaA)‐induced HL produced: 4,5‐, 7,8‐, 9,10‐diols, 1,3‐, 3,6‐quinones, 3‐, 9‐hydroxy and 2 peaks of more polar metabolites. There was a 25‐76% decrease of organo and water‐soluble metabolites in the G6PD‐deficient cells. When HL were incubated with 7,8‐diol, the formation of metabolites mutagenic for Salmonella typhimurium (His‐) was very low in G6PD‐deficient cells. BaP:deoxyadenosine (dAde) and BaP:deoxyaguanosine (dGua) adducts were identified after incubation of both types of HL with BaP. There was a 31‐79% fall in adduct formation by G6PD‐deficient cells. Our results indicate that G6PD‐deficient human lymphocytes are less able to metabolize BaP than normal lymphocytes. We suggest that the NADPH pool is inadequate, in deficient cells, for active BaP metabolism.