The relevance of DNA repair in the cytotoxic response of mammalian cells to alkylating agents

Some experiences on the relevance of the DNA repair mechanisms in the sensitivity of mammalian cells to alkylating agents are illustrated. Using mouse tumor cell lines we showed an interesting correlation between O6-alkylguanine repair, reduced cross-link formation, and resistance to antineoplastic drugs like chloroethylnitrosoureas. The same lines displayed cross-resistance to a methylating monomethyltriazene indicating a possible role of O6-methylguanine in the toxicity of alkylating agents. In other studies we characterized some modified tissues (nodules) developed during hepatic chemical carcinogenesis in the rat. Such hyperplastic nodules displayed higher DNA repair ability, in keeping with their resistant phenotype against toxic and carcinogenic compounds. Both approaches, using cells in culture or animals, gave interesting hints suggesting future developments which may be useful in the understanding of cell transformation mechanisms as well as in cancer chemotherapy.