DNA damage in the central nervous system of rats after in vivo exposure to chemical carcinogens: correlation with the induction of brain tumors.

The alkaline elution technique has been used to evaluate DNA damage in brain of rats treated with a single equimolar dose of 14 carcinogens of different chemical structure. A clear-cut increase of DNA elution rate, which is considered indicative of DNA fragmentation, was produced by 10 compounds known to induce the development of tumors in the rat central nervous system: N-nitroso-N-methylurea, N-nitroso-N-ethylurea, N-nitroso-N-butylurea, N-nitroso-N-methylurethane, methyl methanesulfonate, ethyl methanesulfonate, dimethyl sulfate, diethyl sulfate, 1,3-propansultone, and procarbazine. Similar amounts of DNA fragmentation were produced by both potent and weak brain carcinogens. In contrast, any significant increase of DNA elution rate was absent in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine, N-nitrosodimethylamine, N-nitrosodiethylamine, and beta-propiolactone, all of which are devoid of carcinogenic activity for the rat central nervous system. These results suggest that the described in vivo brain DNA damage/alkaline elution assay deserves further studies on a wide number of carcinogens and noncarcinogens aimed to establish its possible usefulness for a qualitative preliminary assessment of the ability of a compound to induce neurogenic tumors.