title: A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.
abstract: 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.
mesh_terms: 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*
chemical_list: D001391:Azo Compounds; D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D008746:Methylazoxymethanol Acetate; D004247:DNA; D019813:1,2-Dimethylhydrazine