Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene.
Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.
Department of Internal Medicine, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, Missouri.
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D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D002338:Carotenoids / Q000627:therapeutic use*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana; D014801:Vitamin A / Q000032:analysis / Q000097:blood; D014802:Vitamin A Deficiency / Q000150:complications / Q000209:etiology* / Q000517:prevention & control; D019207:beta Carotene
D001580:Benzopyrenes; D012906:Smoke; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids