Carcinogenic potency in rodents versus genotoxic potency in E. coli: a correlation analysis for bifunctional alkylating agents.
The mutagenic (M), recombinagenic (R) and SOS inducing (I) potencies of 6 bifunctional directly acting alkylating agents (mitomycin C, thiotepa, chlorambucil, nitrogen mustard, bis(2-chloroethyl)ether and bis(2-chloroethyl)nitrosourea) were measured in an E. coli test system (E. coli multitest) as the integral under the yield-dose curve obtained for each event. This potency corresponds to the cumulative yield of the affected cell population over the entire effective dose range of the chemical treatment. A weak mutagenic activity was detected only for mitomycin C and thiotepa. Except for bis(2-chloroethyl)ether, all agents were recombinagenic and SOS inducing. When the 3 genotoxic potencies (M, R and I) of these bifunctional alkylating agents were correlated, separately or in combination, with the respective carcinogenic potencies in rodents, a highly significant correlation was obtained with both the recombinagenic and SOS inducing potencies.
Quinto
I
I
Institute of Cellular and Molecular Biochemistry, Naples University Medical School, Italy.
Radman
M
M
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004926:Escherichia coli / Q000235:genetics*; D009152:Mutagenicity Tests / Q000592:standards*; D011995:Recombination, Genetic / Q000187:drug effects; D012377:Rodentia / Q000235:genetics*; D013014:SOS Response, Genetics / Q000187:drug effects
D000477:Alkylating Agents; D002273:Carcinogens; D004247:DNA