Reactions of beta-carotene with cigarette smoke oxidants. Identification of carotenoid oxidation products and evaluation of the prooxidant/antioxidant effect.
Recent intervention trials reported that smokers given dietary beta-carotene supplementation exhibited an increased risk of lung cancer and overall mortality. beta-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. We have examined the interactions of cigarette smoke with beta-carotene in model systems. Both whole smoke and gas-phase smoke oxidized beta-carotene in toluene to several products, including carbonyl-containing polyene chain cleavage products and beta-carotene epoxides. A major product of the reaction was identified as 4-nitro-beta-carotene, which was formed by nitrogen oxides in smoke. Both cis and all-trans isomers of 4-nitro-beta-carotene were detected. The hypothesis that smoke-driven beta-carotene autoxidation exerts prooxidant effects was tested in a liposome system. Lipid peroxidation in dilinoleoylphosphatidylcholine liposomes exposed to gas-phase smoke was modestly inhibited by the incorporation of 0.1 mol % beta-carotene. Both the lipid soluble antioxidant alpha-tocopherol and the water soluble antioxidant ascorbate were oxidized more slowly by gas-phase smoke exposure in liposomes containing beta-carotene. These data indicate that beta-carotene exerts weak antioxidant effects against smoke-induced oxidative damage in vitro. It is unlikely that a prooxidant effect of beta-carotene occurs under biologically relevant conditions or is responsible for an increased incidence of lung cancer observed in smokers who consume beta-carotene supplements.
Baker
D L
DL
Department of Pharmacology and Toxicology, College of Pharmacy, and Department of Chemistry, University of Arizona, Tucson, Arizona 85721-0207, USA.
Krol
E S
ES
Jacobsen
N
N
Liebler
D C
DC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000378:metabolism*; D002417:Cattle; D019587:Dietary Supplements; D005069:Evaluation Studies as Topic; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000209:etiology / Q000401:mortality; D016877:Oxidants / Q000009:adverse effects*; D010084:Oxidation-Reduction; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013329:Structure-Activity Relationship; D014050:Toluene; D019207:beta Carotene / Q000627:therapeutic use*
D000975:Antioxidants; D008081:Liposomes; D016877:Oxidants; D019207:beta Carotene; D002338:Carotenoids; D014050:Toluene