Modulation of the mutagenic activity of cigarette smoke, cigarette smoke condensate and benzo[a]pyrene in vitro and in vivo.
A series of naturally occurring compounds were tested for the ability to modulate the mutagenicity induced by cigarette smoke (CS), cigarette smoke condensate (CSC) and benzo[a]pyrene (BP) in the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow. Sodium selenite, retinol acetate and alpha-tocopherol significantly decreased the mutagenic activity of CS in Salmonella typhimurium TA98. Ascorbic acid, reduced glutathione (GSH), cysteine, caffeine, theophylline, cobalt chloride, folic acid, adenine, adenosine, guanosine, cytidine and cytosine were conversely devoid of any significant effect. Sodium selenite slightly decreased the mutagenic activity of CSC in the same bacterial strain, while caffeine was ineffective and ascorbic acid potentiated its mutagenicity. Ascorbic acid inhibited the mutagenic activity of BP in S. typhimurium TA98, but not in TA100. Retinol acetate diminished the number of BP-induced his+ revertants in TA98 but only at the highest concentrations used, whereas alpha-tocopherol, GSH, cysteine, sodium selenite and caffeine had no effect. Selenite and GSH, which were ineffective when applied individually, inhibited in a dose-dependent manner the BP-induced mutagenesis in S. typhimurium TA98 when simultaneously added to the top agar. All other combinations tested, including selenite plus either GSH, cysteine or caffeine towards CS or CSC, or selenite plus cysteine, or selenite plus retinol acetate and alpha-tocopherol towards BP, failed to produce interactive effects. Sodium selenite and caffeine, given either alone or in combination in drinking water, did not influence the clastogenesis induced in mouse bone marrow by a single treatment with CS or BP. Ascorbic acid was also ineffective towards CS clastogenicity but significantly decreased the number of micronucleated polychromatic erythrocytes induced by BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Balansky
R
R
National Centre of Oncology, Sofia, Bulgaria.
Mircheva
Z
Z
Blagoeva
P
P
D000818:Animals; D016587:Antimutagenic Agents; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D003545:Cysteine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015162:Micronucleus Tests; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D010947:Plants, Toxic; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D018038:Sodium Selenite / Q000494:pharmacology*; D014026:Nicotiana; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014801:Vitamin A / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D016587:Antimutagenic Agents; D012906:Smoke; D014028:Tobacco Smoke Pollution; D014801:Vitamin A; D014810:Vitamin E; D001564:Benzo(a)pyrene; D005978:Glutathione; D018038:Sodium Selenite; D003545:Cysteine; D001205:Ascorbic Acid