Lipid peroxidation and benzo[a]pyrene activation to mutagenic metabolites: in vivo influence of vitamins A, E and C and glutathione in both dietary vitamin A sufficiency and deficiency.
Rats fed with either a sufficient-vitamin A or a vitamin A-free diet were pretreated with 750 mg/kg body weight of retinyl palmitate, alpha-tocopherol acetate, ascorbic acid or glutathione. Benzo[a]pyrene (BaP) metabolism and BaP-induced mutagenesis in Salmonella typhimurium TA98 were investigated and related to lipid peroxidation activities in postmitochondrial (S9) liver fraction. The microsomal mixed-function oxidase activities were decreased by vitamin A deficiency and weakly affected by scavenger treatment. The rate of lipid peroxidation of microsomal membranes was unaffected by vitamin A deficiency because of decreased polyunsaturated fatty acids and increased vitamin E contents. However, lipid peroxidation was decreased by pretreatment with fat-soluble vitamins (chiefly vitamin E) and increased by ascorbic acid. Within each experimental group both BaP metabolism and BaP mutagenic activity were closely correlated with the rate of lipid peroxidation. In vitamin A deficiency, the increased BaP metabolism and mutagenicity could be related to a decrease in cytosolic contents of scavengers (vitamin A and glutathione). In Ames test conditions, the free radical pathway became a route for BaP metabolism and thus the BaP activation to mutagenic metabolites is related to the cellular status in free radical scavengers.
Colin
C
C
Laboratoire de Toxicologie Alimentaire, Université de Bordeaux Talence, France.
Narbonne
J F
JF
Migaud
M L
ML
Grolier
P
P
Cassand
P
P
Pellissier
M A
MA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000009:adverse effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis; D005978:Glutathione / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006128:Growth / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects; D009152:Mutagenicity Tests; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D014801:Vitamin A / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D005227:Fatty Acids; D014801:Vitamin A; D014810:Vitamin E; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D005978:Glutathione; D001205:Ascorbic Acid