Kagawa M, Hakoi K, Yamamoto A, Futakuchi M, Hirose M
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1993 Nov;84(11):1120-9. doi: 10.1111/j.1349-7006.1993.tb02811.x.
Reversibility of forestomach lesions induced by genotoxic and non-genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8-nitroquinoline, dietary 0.4-0.2% 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N-methyl-N'-nitro-N-nitrosoguanidine once a week, or 20 ppm N-methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4-methoxyphenol in the diet as a non-genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non-genotoxic carcinogens clearly regressed after cessation of insult. SPH labeling indices in the non-genotoxic carcinogen-treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non-genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non-genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas.
对遗传毒性致癌物和非遗传毒性致癌物诱导的前胃病变的可逆性进行了组织病理学比较。将30至33只雄性F344大鼠分为几组，分别给予含0.1% 8-硝基喹啉的饮食、含0.4 - 0.2% 2-(2-呋喃基)-3-(5-硝基-2-呋喃基)丙烯酰胺的饮食、每周一次20 mg/kg体重的N-甲基-N'-硝基-N-亚硝基胍灌胃剂量，或饮用水中20 ppm的N-甲基亚硝基脲作为遗传毒性致癌物，或饮食中2%的丁基羟基茴香醚、2%的咖啡酸、2%的芝麻酚或2%的4-甲氧基苯酚作为非遗传毒性致癌物，持续24周。每组10或11只大鼠在第24周处死。其余大鼠一半仅维持基础饮食24周，另一半给予相同化学物质48周，然后处死。遗传毒性致癌物诱导的前胃病变在去除致癌物后并未消退。相比之下，非遗传毒性致癌物诱导的单纯性或乳头状增生（SPH），而非基底细胞增生（BCH），在停止刺激后明显消退。非遗传毒性致癌物处理组的SPH标记指数在去除致癌刺激后下降，而BCH值无论处理与否都较低。在遗传毒性致癌物处理的大鼠中高发生率观察到的非典型增生（AH），在接受非遗传毒性剂处理的动物中也很明显，即使在停药后，尽管发生率较低。即使没有持续刺激，AH标记指数仍保持较高。这些结果表明，即使对于非遗传毒性致癌物，在强烈的细胞增殖过程中也可能在DNA水平发生可遗传的改变，并导致AH的发展。这种假定的癌前病变可能会进展为产生癌症。
