Numerous epidemiological studies have consistently demonstrated that individuals who eat more fruits and vegetables (which are rich in
carotenoids) and who have higher serum β-
carotene levels have a lower risk of
cancer, especially
lung cancer. However, two human intervention trials conducted in Finland and in the United States have reported contrasting results with high doses of β-
carotene supplementation increasing the risk of
lung cancer among smokers. The failure of these trials to demonstrate actual efficacy has resulted in the initiation of animal studies to reproduce the findings of these two studies and to elucidate the mechanisms responsible for the harmful or protective effects of
carotenoids in lung
carcinogenesis. Although these studies have been limited by a lack of animal models that appropriately represent human
lung cancer induced by cigarette
smoke, ferrets and A/J mice are currently the most widely used models for these types of studies. There are several proposed mechanisms for the protective effects of
carotenoids on cigarette
smoke-induced lung
carcinogenesis, and these include
antioxidant/prooxidant effects, modulation of
retinoic acid signaling pathway and metabolism, induction of
cytochrome P450, and molecular signaling involved in cell proliferation and/or apoptosis. The technical challenges associated with animal models include strain-specific and diet-specific effects, differences in the absorption and distribution of
carotenoids, and differences in the interactions of
carotenoids with other
antioxidants. Despite the problems associated with extrapolating from animal models to humans, the understanding and development of various animal models may provide useful information regarding the protective effects of
carotenoids against lung
carcinogenesis.