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 β-carotene. A major area of concern in the design of long-term, large-scale population studies to ascertain the efficacy of such...
| Published in: | Canadian Journal of Physiology and Pharmacology |
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| Main Authors: | , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Canadian Science Publishing
1987
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1139/y87-083 http://www.nrcresearchpress.com/doi/pdf/10.1139/y87-083 |
| Summary: | 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 β-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 β-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. Whether agents effective using these end points will also produce a response in preventing or reversing premalignant lesions is currently under investigation. |
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