Cell proliferation and formaldehyde-induced respiratory carcinogenesis.
Cell proliferation and formaldehyde-induced respiratory carcinogenesis.
复制标题
细胞增殖和甲醛诱导的呼吸道癌发生。
作者：
T. Monticello;Kevin T. Morgan
甲醛是一种大鼠鼻腔致癌物质，但这种化学物质对人类的致癌风险仍有待确定。甲醛诱导鼻上皮细胞增殖和DNA-蛋白质交联形成短期暴露后的非线性，浓度依赖性增加。在这篇综述中提出的是从一个机械为基础的甲醛吸入研究的结果，其中一个重要的终点是在鼻肿瘤诱导的靶部位的细胞增殖指数的测量。雄性Fischer 344大鼠暴露于0、0.7、2、6、10或15 ppm甲醛长达2年（6小时/天，5天/周）。细胞增殖的统计学显著性增加仅限于10和15 ppm组，其在整个研究期间保持升高。细胞增殖的浓度依赖性增加与肿瘤反应曲线密切相关，支持细胞增殖持续增加是甲醛致癌作用的重要组成部分的提议。在甲醛诱导的啮齿动物鼻癌中观察到的非线性与靶器官再生细胞增殖的高浓度效应以及甲醛的遗传毒性效应一致。这些研究的细胞动力学数据提供了重要的信息，可用于评估人类暴露于甲醛的风险。
Formaldehyde is a nasal carcinogen in the rat but the cancer risk this chemical poses for humans remains to be determined. Formaldehyde induces nonlinear, concentration-dependent increases in nasal epithelial cell proliferation and DNA-protein cross-link formation following short-term exposure. Presented in this review are results from a mechanistically based formaldehyde inhalation study in which an important endpoint was the measurement of cell proliferation indices in target sites for nasal tumor induction. Male Fischer 344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 2 years (6 hr/day, 5 day/week). Statistically significant increases in cell proliferation were confined to the 10 and 15 ppm groups, which remained elevated throughout the study. The concentration-dependent increases in cell proliferation correlated strongly with the tumor response curve, supporting the proposal that sustained increases in cell proliferation are an important component of formaldehyde carcinogenesis. The nonlinearity observed in formaldehyde-induced rodent nasal cancer is consistent with a high-concentration effect of regenerative cell proliferation of the target organ coupled with the genotoxic effects of formaldehyde. Cell kinetic data from these studies provide important information that may be utilized in the assessment of risk for humans exposed to formaldehyde.
影响因子：
3.8
作者：
Ion G;Akinsete JA;Hardman WE
通讯作者：
Hardman WE
影响因子：
11.2
作者：
Lawrence A. Loeb
通讯作者：
Lawrence A. Loeb
影响因子：
11.2
作者：
S. Cohen;L. Ellwein
通讯作者：
S. Cohen;L. Ellwein