UBC Theses and Dissertations
A short term in vivo bioassay for the organ specificity of carcinogens Koropatnick, D. James
The possibility of using alkaline sucrose gradient analysis of the digestive tract tissue of mice to investigate the carcinogenic potential of organotropic compounds was examined. Young Swiss mice were injected with ³H-TdR to label the DNA of the epithelial cells of the digestive tract. Thirty h later they were force-fed carcinogenic or non-carcinogenic chemicals. Tissue samples were taken four h post-treatment and hydrolyzed on top of the alkaline sucrose gradient. Shifts in sedimentation profiles indicated that: (1) both cultured human fibroblasts and epithelial cells of the gastrointestinal system show a shift in sedimentation profile after treatment with the carcinogen MNNG that is taken to indicate repair; (2)- the carcinogen 4-nitroquinoline 1-oxide (4NQO) and 6-methyl 4NQO cause DNA fragmentation in the epithelial cells of the gastrointestinal system while the non-carcinogen 6NQO lacks this capacity; (3) the ultimate carcinogen N-acetoxy 2AAF caused DNA fragmentation in esophagus and stomach cells while the precarcinogen 2AAF produced no significant effect; (4) only the carcinogenic nitrosation products of methylguanidine damaged the DNA of gastric epithelial cells; (5) the precarcinogens 2AAF and DMN produced DNA fragmentation in the main target organ -the liver -but had little effect on the epithelial cells of the stomach; and (6) extracts of the carcinogenic plant pteridium aquilinvjn (bracken fern) showed an organotropic DNA-fragmenting ability in vivo and in vitro that corresponded to its .organ-specific tumour induction in cattle and rats. Treatment with heat appears to drastically reduce the DNA-fragmenting ability of the plant. The results suggest that the application of the sucrose gradient technique to the epithelial cells of esophagus, stomach and liver of pre-labelled (³H-TdR) and force-fed young mice incorporates the advantages of in vitro short term bioassays with the completeness of tests using whole mammals.
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