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), cigarett e smoke condensate (CSC) and benzo[a]pyrene (BP) in the Salmonella/mic rosome mutagenicity assay and the micronucleus test in mouse bone marr ow. Sodium selenite, retinol acetate and alpha-tocopherol significantl y decreased the mutagenic activity of CSC in Salmonella typhimurium TA 98. Ascorbic acid, reduced glutathione (GSH), cysteine, caffeine, theo phylline, 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 mutage nic activity of BP in S. typhimurium TA98, but not in TA100. Retinol a cetate diminished the number of BP-induced his(+) revertants in TA98 b ut only at the highest concentrations used, whereas alpha-tocopherol, GSH, cysteine, sodium selenite and caffeine had no effect. Selenite an d GSH, which were ineffective when applied individually, inhibited in a dose-dependent manner the BP-induced mutagenesis in S. typhimurium T A98 when simultaneously added to the top agar. All other combinations tested, including selenite plus either GSH, cysteine or caffeine towar ds CS or CSC, or selenite plus cysteine, or selenite plus retinol acet ate and cr-tocopherol towards BP, failed to produce interactive effect s. Sodium selenite and caffeine, given either alone or in combination in drinking water, did not influence the clastogenesis induced in mous e bone marrow by a single treatment with CS or BP. Ascorbic acid was a lso ineffective towards CS clastogenicity but significantly decreased the number of micronucleated polychromatic erythrocytes induced by BP. A strong protective effect in this assay was observed in mice treated with BP plus GSH or cysteine. Out of the agents tested, sodium seleni te, vitamins A, C and E, GSH and cysteine seem to be the most promisin g inhibitors of the in vitro or in vivo mutagenic activity of CS and B P.