A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.
Comparative analysis of the cytotoxicity, transformation efficiency, induction of alkali labile sites (ALS) and DNA methylation in human foreskin fibroblasts was carried out with two dimethylhydrazine (DMH) regioisomers (1,1-DMH and 1,2-DMH) and the acetate (A) derivative of the metabolite methylazoxymethanol (MAM) of 1,2-DMH. Effective ED50 cytotoxic doses for MAMA, 1,1-DMH and 1,2-DMH were 0.056, 6.83 and 6.30 mM, respectively. MAMA and 1,1-DMH were more effective transformers than 1,2-DMH. However, methylation of purines accounted for less than 1% of the total radiolabel associated with DNA for all 3 agents. 1,2-DMH, 1,1-DMH and MAMA induced O6MeGua/N7MeGua ratio of 0.04, 0.32 and 0.18, respectively. Only MAMA induced measurable alkali labile lesions at transforming doses. These results suggest that other mechanisms may play a role in the initiation of transformation events by hydrazine analogues.
D019813:1,2-Dimethylhydrazine; D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004127:Dimethylhydrazines / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008745:Methylation; D008746:Methylazoxymethanol Acetate / Q000633:toxicity*; D008763:Methylhydrazines / Q000633:toxicity*
D001391:Azo Compounds; D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D008746:Methylazoxymethanol Acetate; D004247:DNA; D019813:1,2-Dimethylhydrazine