Decreased excretion of thioethers in urine of smokers after the use of β-carotene

Abstract
Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, β-carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of β-carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of β-carotene by smokers would affect urinary thioether excretion. Before the intervention the β-carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3mmolSH/molcreatinine). During the intervention (20 mg β-carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the β-carotene group showed a 5% decrease (P=0.004). After the intervention the β-carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmol SH/mol creatinine; P=0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of β-carotene. This latter observation suggests a role of β-carotene in the detoxification of tobacco smoke constituents. Our observations warrant further studies on the involvement of β-carotene in the generation and detoxification of electrophilic intermediates.