A possible mechanism for the dose-response relationship observed for renal mesenchymal tumours induced in the rat by a single dose of N-nitrosodimethylamine.
The incidence of renal mesenchymal tumours induced in rats by N-nitrosodimethylamine (NDMA) is related to the dose in a sigmoidal dose-response curve. Each kidney bears only one or two tumours at 20-24 months. In contrast, one week after dosing, a large number of preneoplastic proliferative foci is present, the incidence of which is linearly related to dose and directly proportional to methylation of DNA by NDMA. It is suggested that most of these foci are removed by host defense mechanisms before they can progress to tumour, thus accounting for the sigmoid shape of the dose-response curve for the tumours.
Driver
H E
HE
MRC Toxicology Unit, Carshalton, Surrey, UK.
White
I N
IN
Steven
F S
FS
Butler
W H
WH
D000818:Animals; D004128:Dimethylnitrosamine; D004305:Dose-Response Relationship, Drug; D007680:Kidney Neoplasms / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344
D004128:Dimethylnitrosamine