EFFECTS OF BETA-CAROTENE AND ALPHA-TOCOPHEROL ON PHOTOGENOTOXICITY INDUCED BY 8-METHOXYPSORALEN - THE ROLE OF OXYGEN

The protective effect of beta-carotene (beta-C) and alpha-tocopherol ( alpha-T), singularly and in equimolar mixtures, toward the photomutage nicity induced by 8-methoxypsoralen (8-MOP), at different oxygen parti al pressure (pO(2)), was evaluated in two different experimental model s: Salmonella typhimurium TA102 and Saccharomyces cerevisiae D7, After phototreatment with 8-MOP, the results show a lethal effect under hyp oxic conditions in both experimental model systems, an increase in rev ertants associated to the pO(2) increase in S. typhimurium TA102, and a decrease in revertants and convertants associated to the pO(2) incre ase in S. cerevisiae D7. In S. typhimurium TA102, in atmospheric condi tion, beta-C and alpha-T (1.86 or 18.6 mu M) show a protective effect only at the higher dosage. alpha-T was more protective than beta-C. Th e equimolar mixtures show an antimutagenic effect at both dosage used with a synergistic effect at lower dosage and an additive antimutageni c activity at higher dosage. An inhibition of the spontaneous mutageni city by mixtures at higher dosage was also observed, The results obtai ned in S. typhimurium TA102 show an antimutagenic effects of beta-C, a lpha-T and their mixture at 190 mmHg pO(2), confirming the data obtain ed in air condition. At 380 mmHg pO(2), alpha-T and the mixture show a significant antimutagenic activity; at 570 mmHg pO(2), only alpha-T i s protective. At 760 mmHg pO(2), no protective effect was observed by the two antioxidants, and beta-C increases the photomutagenicity induc ed by 8-MOP. In S. cerevisiae D7 a protective effect was only observed at 380 mmHg pO(2) with the mixture. No antigenotoxic effect was found in the other experimental conditions, even if the uptake of the two a ntioxidants was confirmed by HPLC. Our results underline the role of o xygen in the photomutagenicity induced by 8-MOP and in the antimutagen ic activity of beta-C and alpha-T. This is the first report confirming in a cellular experimental model the data obtained in some chemical s ystems: the protective effect of beta-C only at low pO(2) and the syne rgistic effect of mixture of beta-C and alpha-T.