Use of intermediate endpoints in quantitating the response of precancerous lesions to chemopreventive agents.
A current area of emphasis in cancer research is the determination of whether cancer can be prevented through the use of naturally occurring chemopreventive agents such as beta-carotene. A major area of concern in the design of long-term, large-scale population studies to ascertain the efficacy of such chemopreventive agents lies in the paucity of biological data on the activity of these agents in man. The studies described in this paper were performed to determine whether a series of short-term markers could be used in chemopreventive trials as indicators of the possible success of a chemopreventive regime. Three such markers are described. The first involves the measurement of genotoxic damage in the target tissues of carcinogen-exposed individuals by using the micronucleus test on exfoliated cells. This end point has been successfully used to demonstrate a reduction in carcinogen damage (micronuclei production) in the oral cavity of individuals in population groups at elevated risk for oral cancer (tobacco and betel quid users in the Philippines, snuff users in the Northwest Territories). The second marker involves the determination of DNA adducts in exfoliated cells of carcinogen-exposed individuals by the use of DNA postlabelling procedure. The final marker discussed involves a chemical determination of the levels of a chemopreventive agent in target tissues of individuals receiving a supplement in the diet. In this case, the example described is beta-carotene in exfoliated cells of carcinogen-exposed individuals. These three markers may be combined to determine whether a chemopreventive agent reaches a target tissue, affects DNA adduct formation, and prevents genotoxic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002338:Carotenoids / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000473:pathology; D004247:DNA / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D012176:Retinoids / Q000627:therapeutic use*; D019207:beta Carotene
D002273:Carcinogens; D012176:Retinoids; D019207:beta Carotene; D002338:Carotenoids; D004247:DNA