Modifying effects of carotenoids in a rat multi-organ carcinogenesis model : Inhibition in the liver but promotion of lung tumor development

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To cast experimental light on epidemiological findings regarding adverse effects of β-carotene on human lung neoplasia, rats were administered three carcinogens, diethylnitrosamine (DEN), dihydroxy-di-N-propylnitrosamine (DHPN) and azoxymethane (AOM), within a four week period, for induction of tumors primarily in the liver, lung, colon and kidney (Multi-organ carcinogenesis model), thereafter received vehicle supplementation with lycopene (0.05, 0.01 or 0.005%), β-carotene (0.05, 0.01%), or palm carotene, a mixture of β-carotene (60%) and α-carotene (30%), (0.05, 0.01%) for 40weeks. At the final sacrifice, the number of liver glutathione S-transferase positive lesion, a marker for neoplastic lesions, was significantly reduced by the lycopene at 0.01%, whereas lung tumor area was increased by lycopene (at 0.05 or 0.005%) and β-carotene (0.05%). No influence on lesions of colon and kidney were apparent. The results thus point to organ specific effects of the carotenoids tested in an animal model and the detrimental impact on lung carcinogenesis possibly mirroring reports observed in man. Our results suggests that a more coordinated approach to the influence of chemopreventive agents is necessary, with analysis of mechanisms in animal models as an essential component, before trials are commenced in future.
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