Chemical Carcinogen (Hydrazine, Polynuclear Hydrocarbon and/or Synthetic Jet Fuel Components) Induced Carcinogenesis of Human Cells, In Vitro

摘要

Select chemicals of interest to the Air Force and identified as man made environmental contaminants have been found to neoplastically transform human cells in vitro. Benzo(a)pyrene one of these compounds of interest, exhibits unique features of movement from the extracellular environment to the nucleus of the cell. B(a)P is transported into human foreskin fibroblasts from the plasma membrane to the nucleus by binding as the unmetabolized parent B(a)P. B(a)P forms a low binding association with a lipoprotein complex in the cytoplasm that has a MW of 12,500. The B(a)P following penetration into the nucleus is then oxygenated to various metabolites. Benzo pyrene-diol-epoxide-I has been identified as a metabolite in the nucleus that interacts with deoxy-Guanine to form a DNA adduct, 7R-BPDE-I-dG. We then used another hydrocarbon 1,2,3,4-tetrahydro-7,12-dimethyl benz(a) anthracene to induced carcinogenesis in human cells. To date we have no evidence for extracellular or intracellular metabolism of this compound under conditions for transformation. We conclude tentatively that this data suggests that there is an alternate requirement for polynuclear hydrocarbon induced carcinogenesis in human cells compared to rodent cells. (Author)