Lee T C, Tanaka N, Lamb P W, Gilmer T M, Barrett J C
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Science. 1988 Jul 1;241(4861):79-81. doi: 10.1126/science.3388020.
Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Two arsenic salts (sodium arsenite and sodium arsenate) induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene. The ability of arsenic to induce gene amplification may relate to its carcinogenic effects in humans since amplification of oncogenes is observed in many human tumors. The inability of arsenic to induce gene mutations may relate to the negative results of arsenic in long-term animal studies and suggests that these experiments may not detect some environmental agents that act late in the carcinogenic process in humans.
砷是一种已被充分证实的人类致癌物，但几乎没有证据表明它对动物具有致癌性，并且在小鼠致癌性的两阶段模型中，它作为引发剂或肿瘤促进剂没有活性。两种砷盐（亚砷酸钠和砷酸钠）诱导出了高频率的甲氨蝶呤抗性3T6细胞，这些细胞被证明具有二氢叶酸还原酶基因的扩增拷贝。砷诱导基因扩增的能力可能与其对人类的致癌作用有关，因为在许多人类肿瘤中都观察到了癌基因的扩增。砷不能诱导基因突变可能与砷在长期动物研究中的阴性结果有关，这表明这些实验可能无法检测到某些在人类致癌过程后期起作用的环境因素。
