Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro, Final Report July 1, 1980 - November 30, 1984

摘要

There is data from in vivo animal systems that DMH and polynuclear hydrocarbons may pose a potential carcinogenic risk to man. They are metabolized to reactive intermediate metabolites that are localized in susceptible target sites. These sites may be away from the tissue that activates the proximate carcinogen. One such highly reactive intermediate obtained from DMH metabolism is methylazoxy methanol. This compound purportedly degrades to form methyldimine and formaldehyde. Mehhyldiimine then forms a methyl radical after homolysis. This compound then is converted to a carbonium ion and the radical interacts with the purine bases in DNA. Methylazoxymethanol acetate, (MAMA) in the presence of colon, secum, and liver homogenates reduced NAD+ to NADH. The alcohol dehydrogenase-like enzymes are quite high in activity in the liver and may account for the organotypic response of MAM in animals. We continued biochemical studies to examine how these carcinogens were activated, entered the human cell and were transported to the nculeus. We also studied how these reactive carcinogenic intermediates interacted with different bases in the DNA.