Formation and repair of O6-methylguanine and methylation of the Ha-ras proto-oncogene by N-methyl-N-nitrosourea are not associated with mammary tumor resistance in the Copenhagen rat.
A high incidence of mammary adenocarcinomas is induced in sexually immature, female Buf/N rats by a single dose of N-methyl-N-nitrosourea (MNU). The Ha-ras gene is activated in a majority of these tumors. The Copenhagen (Cop) rat is completely resistant to mammary gland carcinogenesis by a number of carcinogens, including MNU. Here we show that MNU-treated Buf/N and Cop rats do not differ in the extent of formation and rate of repair of O6-methylguanine in DNA isolated from their mammary epithelial cells. Furthermore, we show that the transcriptional activities of the Ha-ras genes are similar in the mammary glands of Buf/N and Cop rats and that the extents of methylation by MNU of restriction fragments containing the Ha-ras gene from mammary gland DNA are not different for the two strains. Resistance of the Cop rat to mammary carcinogenesis, therefore, appears not to be due to a defect in the interaction of the carcinogen with the target DNA.
Lu
S J
SJ
Department of Medical Biophysics, University of Toronto, Canada.
Chaulk
E J
EJ
Archer
M C
MC
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D011905:Genes, ras; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D008745:Methylation; D008770:Methylnitrosourea; D051381:Rats
D004273:DNA, Neoplasm; D006147:Guanine; D008770:Methylnitrosourea; C008449:O-(6)-methylguanine