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

用放射自显影和N-正丁基-N-丁烷-4-醛-亚硝胺(BBN)诱导的F344大鼠膀胱增生细胞，用放射自显影技术测定非程序DNA合成，以评价F344大鼠膀胱发育不良细胞对化学致癌物的DNA修复能力。BBN染毒6、8、10周后摘除大鼠膀胱。在Williams培养液中注射10‘-甲基-N’-硝基-N-亚硝基-N-亚硝基-N-胸腺嘧啶核苷(M-甲基-N‘-硝基-N-亚硝基-N-亚硝基)和[甲基-~(3 H)]胸腺嘧啶核苷，用放射自显影计数细胞核上的颗粒(S期细胞除外)。对MNNG作用的增生性细胞DNA修复水平普遍低于正常移行细胞。长期暴露于BBN的细胞，其DNA修复能力下降更为明显。这一膀胱模型的结果证实了先前关于大鼠肝脏模型…的数据此外，这意味着改变的细胞对DNA损伤的修复是异常的，促进的增殖和受损的DNA修复的组合在癌前细胞向癌细胞的转化中可能是重要的。使用几种化学致癌物和伴随转移癌的肝脏细胞来评估人肝细胞的DNA修复能力。在所检测的化合物中，有5个化合物，即L-硝基-1，3-二硝基，1，8-二硝基-1，8-二硝基和L-硝基-3-乙酰氧基芘明显地引起了DNA修复的阳性反应。在啮齿动物肝细胞DNA修复中呈阳性反应的2，7-二硝基荧烯和3-硝基荧蒽的阴性反应表明，人和大鼠肝细胞对这些物质的代谢活性存在物种差异。本研究的这些结果为分析发育不良的肝细胞如对化学致癌物或紫外线反应的肝硬变的DNA修复能力提供了一种可能性。较少

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