Dependence of benzo(a)pyrene metabolism on NADPH pool in normal and glucose-6-phosphate dehydrogenase deficient human fibroblasts.
Human skin fibroblasts (HSF), from normal donors and donors carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, grown in vitro in the presence of 0.25-5 microM benzo(a)pyrene (BaP), produced the following organic-soluble metabolites: 9,10-diol, 7,8-diol, quinones, 3- and 9-hydroxide and a more polar fraction, and the following water-soluble metabolites: more polar, 3- and 9-hydroxide and 9,10-diol. Single organic- and water-soluble metabolites increased with BaP concentration in both types of HSF, but the ratio normal/variant increased with BaP concentration. NADPH level and NADPH/NADP+ ratio underwent a slight decrease in normal HSF incubated with 2.5 microM BaP, while a greater fall occurred in the deficient HSF at 0.25 and 2.5 microM BaP. NADPH content seems to be rate-limiting for BaP metabolism in the deficient cells.
Pascale
R
R
Istituto di Patologia Generale dell'Università di Sassari, Italy.
Ruggiu
M E
ME
Simile
M M
MM
Daino
L
L
Vannini
G
G
Seddaiu
M A
MA
Satta
G
G
Feo
F
F
D000328:Adult; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000378:metabolism*
D001564:Benzo(a)pyrene; D009249:NADP; D003577:Cytochrome P-450 Enzyme System