Experimental Studies on the Carcinogenicity of Man Made Fibers

对雌性叙利亚仓鼠经口给予闪石石棉、铁石棉和青石棉两年后进行组织学观察，以评价六种精细人造纤维的致瘤性。事实证明，某些类型的人造纤维具有比石棉更大的诱发肿瘤的潜力。此外，作为人造纤维组中的具体观察结果，在胸膜内器官而不是胸膜腔诱导肿瘤。由于胸膜增厚与仓鼠间皮瘤的发生率之间没有关系，因此推测胸膜增厚可能是由与纤维材料致瘤性不同的机制引起的。我们通过测定体外几种条件下8-羟基-2 '-脱氧鸟苷（oh^8dG）的产率，比较了石棉和人造纤维对DNA的攻击潜力。实验结果表明，石棉对DNA有损伤作用，并可导致oh^8dG的点突变，在一定条件下，几种人造纤维对DNA的损伤作用与石棉相似。结果表明，癌症的风险可能与微量元素和必需元素的摄入量有关。我们还测定了暴露于2-硝基丙烷的雄性Sprague道利大鼠再生肝（部分肝切除后24、48、72小时和7天）细胞核DNA中oh ^8 dG的含量，以验证部分肝切除后对致癌物的高度敏感性是细胞增殖阶段DNA损伤敏感性的原因这一假设。提示增殖细胞中的核DNA，例如，细胞在纤维材料的连续细胞损伤中，处于对活性氧的外源性攻击的敏感阶段。

Histological observations were performed on female Syrian hamsters two years after the intratracheal administration of amphibole asbestos, amosite and crocidolite, to evaluate the tumorigenicity of six types of fine man-made fibers. It was demonstrated that some type of man-made fibers had a potency to induce tumors much more than asbestos. Moreover, as a specific observation in man-made fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. It was suggested that the thickening of visceral pleura might be induced by a different mechanism from the tumorigenicity of fibrous materials, since there was no relation between the pleural thickening and mesothelioma incidence in hamsters.We compared the potential of asbestos and man-made fibers to attack DNA by the determination of the yield of 8-hydroxy-2'-deoxyguanosine (oh^8dG) in several conditions in vitro. It was suggested by the result that asbestos could damage DNA which resulted in oh^8dG as a cause of point mutation and also several types of man-made fibers had similar effects as asbestos under certain conditions.Rats(Wistar, female, 4 week-old) were fed iron-deficient or manganese and copper-deficient diets for 8 weeks to determine the oxidative damage of DNA in element deficiency. Results suggest that the risk of cancer may be associated with the minor and essential element intake. We also determined the amount of oh^8dG in the nuclear DNA of regenerating liver (24, 48, 72 hours and 7 days after partial hepatectomy) of male Sprague Dawley rats exposed to 2-nitropropane for the verification of a hypothesis that a high sensitivity to carcinogens after partial hepatectomy is responsible for the sensitivity of DNA damage in the cell proliferating stage. It is suggested that nuclearDNA in a proliferating cells, e.g., cells in continuous cell damage by fibrous materials, is in a sensitive stage to exogenous attack by active oxygen species.