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Science 8 January 1993:
Vol. 259. no. 5092, pp. 219 - 222
DOI: 10.1126/science.8421782
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Articles

Science, Vol 259, Issue 5092, 219-222
Copyright © 1993 by American Association for the Advancement of Science

articles

The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase

LL Dumenco, E Allay, K Norton, and SL Gerson

Department of Medicine, University Hospitals of Cleveland, OH.

Nitrosoureas form O6-alkylguanine-DNA adducts that are converted to G to A transitions, the mutation found in the activated ras oncogenes of nitrosourea-induced mouse lymphomas and rat mammary tumors. These adducts are removed by the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Transgenic mice that express the human homolog of this protein in the thymus were found to be protected from developing thymic lymphomas after exposure to N-methyl-N-nitrosourea. Thus, transgenic expression of a single human DNA repair gene is sufficient to block chemical carcinogenesis. The transduction of DNA repair genes in vivo may unravel mechanisms of carcinogenesis and provide therapeutic protection from known carcinogens.


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