Pathological study on the capability for DNA repair of cells in dysplastic epithelium

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Assessment of DNA repair capability of dysplastic cells of urinary bladder responding tochemical carcinogen was done by measurement of unscheduled DNA syntheses using autoradiograph and hyperplastic cells induced by N-n-butyl-N-butan-4-al-nitrosamine (BBN) in F344 rats. Urinary bladder was removed from rats given BBN for 6 or 8 or 10 weeks. Organ culture of the bladder injected of 10^<-3>M N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and [Methyl-^3H]thymidine was performed in the Williams Medium E. Unscheduled DNA synthesis was measured by counting autoradiographic grains on the nucleus (S phase cells were excluded for the counting). DNA repair level in the hyperplastic cells responding to the exposure to MNNG was generally lower than that in normal transitional cells. The reduced DNA repair capability of the hyperplastic cells was more prominent in the cells exposed to BBN for longer term. The results obtained in this urinary bladder model comfirmed the previous data on rat liver model … More , implying that the repair of DNA damage by the altered cells is abnormal and the combination of enhanced proliferation and impaired DNA repair may be important in the conversion of precancerous cells to cancer cells.DNA repair capability of human hepatocytes was assessed using several chemical carcinogens and cells from the livers accompanying metastatic carcinomas. Out of the tested compounds, 5 compounds, i.e., l-nitropyrene, 1,3-dinitropyrene, 1,8-dinitropyrene and l-nitro-3 acetoxypyrene, clearly elicited positive responses of DNA repair. The negative responses of 2,7-dinitrofluorene and 3-nitrofluoranthene, which had been positive in DNA repair with rodent hepatocytes, suggest some species differences between humans and rats in the metabolic activity of hepatocytes toward these agents. These results in the present study suggest a possibility for the analysis of DNA repair capability in the dysplastic hepatocytes such as in liver cirrhosis responding to chemical carcinogens or ultra-violet. Less