The effect of low and high doses of beta-carotene and exposure to cigarette smoke on the lungs of ferrets.

When the diets of ferrets were supplemented with large (pharmacologic) daily doses of beta-carotene (BC) for 6 months, the levels of retinoic acid and the retinoic acid receptor beta declined significantly in lung tissues. Indicators of cell proliferation (c-jun and c-fos proteins and others) increased. Histologic observations showed that feeding high doses of BC resulted in keratinized squamous metaplasia in the lung tissues. When high-doses of BC were combined with daily exposure to cigarette smoke, the BC effects were greatly accentuated. These results may lead to an explanation of the increased incidence of lung cancer in two large independent epidemiologic studies of smokers in which pharmacologic doses of BC were given.