Promutagenic lesions persist in the DNA of target cells for nitrosamine-induced carcinogenesis.
Immunohistochemical procedures for the location of O6-methylguanine (O6-meGua) permit detection of cells proficient for the metabolism of N-nitrosodimethylamine (NDMA) and deficient for the repair of this DNA lesion. Such cells are potentially at high risk for cancer induction and are present in various tissues. In animals maintained on a protein-deficient diet, the distribution and intensity of alkylation of individual cells is altered, particularly in liver where fewer cells apparently retain the capacity to metabolize the nitrosamine, thereby permitting increased levels of alkylation in other tissues. In the renal cortex, specific, O6-meGua-positive target cells for renal cancer induced by a single dose of NDMA in weanling rats persist at least up to the appearance of early lesions. Persistence of alkylated cells in several tissues indicates prospects for the detection of environmental exposure.
Fan
C Y
CY
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, UK.
Butler
W H
WH
O'Connor
P J
PJ
D000478:Alkylation; D000818:Animals; D004249:DNA Damage; D004128:Dimethylnitrosamine / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats
D006147:Guanine; C008449:O-(6)-methylguanine; D004128:Dimethylnitrosamine