Dual role of beta-carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2.

Results from some intervention trials indicated that\r\nsupplemental b-carotene enhanced lung cancer incidence\r\nand mortality in chronic smokers. The aim of this study\r\nwas to verify the hypothesis that high concentrations of\r\nthe carotenoid, under the pO2 present in lung (100–150\r\nmmHg), may exert deleterious effects through a prooxidant\r\nmechanism. To test this hypothesis, we examined the\r\ninteractions of b-carotene and cigarette smoke condensate\r\n(tar) on the formation of lipid peroxidation products in rat\r\nlung microsomal membranes enriched in vitro with\r\nvarying b-carotene concentrations (from 1 to 10 nmol/\r\nmg prot) and then incubated with tar (6–25 mg/ml) under\r\ndifferent pO2. As markers of lipid peroxidation, we\r\nevaluated the levels of conjugated dienes and malondialdehyde,\r\npossessing mutagenic and pro-carcinogenic activity.\r\nThe exposure of microsomal membranes to tar\r\ninduced a dose-dependent enhancement of lipid peroxidation,\r\nwhich progressively increased as a function of pO2.\r\nUnder a low pO2 (15 mmHg), b-carotene acted clearly as\r\nan antioxidant, inhibiting tar-induced lipid peroxidation.\r\nHowever, the carotenoid progressively lost its antioxidant\r\nefficiency by increasing pO2 (50–100 mmHg) and acted as\r\na prooxidant at pO2 ranging from 100 to 760 mmHg in a\r\ndose-dependent manner. Consistent with this finding, the\r\naddition of a-tocopherol (25 mM) prevented the prooxidant\r\neffects of the carotenoid. b-Carotene auto-oxidation,\r\nmeasured as formation of 5,6-epoxy-b,b-carotene, was\r\nfaster at high than at low pO2 and the carotenoid was\r\nmore rapidly consumed in the presence of tar. These data\r\npoint out that the carotenoid may enhance cigarette\r\nsmoke-induced oxidative stress and exert potential deleterious\r\neffects at the pO2 normally present in lung tissue.