Effects of β-carotene and α-tocopherol on photogenotoxicity induced by 8-methoxypsoralen: The role of oxygen

The protective effect of β-carotene (β-C) and α-tocopherol (α-T), singularly and in equimolar mixtures, toward the photomutagenicity induced by 8-methoxypsoralen (8-MOP), at different oxygen partial pressure (pO₂), was evaluated in two different experimental models: Salmonella typhimurium TA102 and Saccharomyces cerevisiae D7. After phototreatment with 8-MOP, the results show a lethal effect under hypoxic conditions in both experimental model systems, an increase in revertants associated to the pO₂ increase in S. typhimurium TA102, and a decrease in revertants and convertants associated to the pO₂ increase in S. cerevisiae D7. In S. typhimurium TA102, in atmospheric condition, β-C and α-T (1.86 or 18.6 μM) show a protective effect only at the higher dosage. α-T was more protective than β-C. The equimolar mixtures show an antimutagenic effect at both dosage used with a synergistic effect at lower dosage and an additive antimutagenic activity at higher dosage. An inhibition of the spontaneous mutagenicity by mixtures at higher dosage was also observed. The results obtained in S. typhimurium TA102 show an antimutagenic effects of β-C, α-T and their mixture at 190 mmHg pO₂, confirming the data obtained in air condition. At 380 mmHg pO₂, α-T and the mixture show a significant antimutagenic activity; at 570 mmHg pO₂, only α-T is protective. At 760 mmHg pO₂, no protective effect was observed by the two antioxidants, and β-C increases the photomutagenicity induced by 8-MOP. In S. cerevisiae D7 a protective effect was only observed at 380 mmHg pO₂ with the mixture. No antigenotoxic effect was found in the other experimental conditions, even if the uptake of the two antioxidants was confirmed by HPLC. Our results underline the role of oxygen in the photomutagenicity induced by 8-MOP and in the antimutagenic activity of β-C and α-T. This is the first report confirming in a cellular experimental model the data obtained in some chemical systems: the protective effect of β-C only at low pO₂ and the synergistic effect of mixture of β-C and α-T.