β-Carotene and lung cancer in smokers

β-Carotene and lung cancer in smokers

Chronic high doses of β-carotene supplementation increases the probability of lung cancer in cigarette smokers according to a study, although the validity of this statement has been put into question.^{[26][unreliable source?][27]} The effect is specific to supplementation dose as no lung damage has been detected in those who are exposed to cigarette smoke and who ingest a physiologic dose of β-carotene (6 mg), in contrast to high pharmacologic dose (30 mg). Therefore, the oncology from β-carotene is based on both cigarette smoke and high daily doses of β-carotene.^[28] There have been at least two suggestions for the mechanism for the observed harmful effect of high-dose β-carotene supplementation in this group. None has so-far gained wide acceptance.

A common explanation of the high dose effect is that when retinoic acid is liganded to RAR-beta (retinoic acid receptor beta), the complex binds AP1 (activator protein 1). AP1 is a transcription factor that binds to DNA and in downstream events promote cell proliferation. Therefore, in the presence of retinoic acid, the retinoic acid:RAR-beta complex binds to AP1 and inhibits AP-1 from binding to DNA. In that case, AP1 is no longer expressed, and cell proliferation does not occur. Cigarette smoke increases the asymmetric cleavage of β-carotene, decreasing the level of retinoic acid significantly. This can lead to a higher level of cell proliferation in smokers, and consequently, a higher probability of lung cancer.

Another β-carotene breakdown product suspected of causing cancer at high dose is trans-β-apo-8'-carotenal (common apocarotenal), which has been found in one study to be mutagenic and genotoxic in cell cultures which do not respond to β-carotene itself

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