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  • 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.
    Author: Kumari HL, Kamat PL, D'Ambrosio SM, Witiak DT, Milo GE.
    Journal: Cancer Lett; 1985 Dec; 29(3):265-75. PubMed ID: 4075295.
    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.
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