Nikula K J, Snipes M B, Barr E B, Griffith W C, Henderson R F, Mauderly J L
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185, USA.
Fundam Appl Toxicol. 1995 Apr;25(1):80-94. doi: 10.1006/faat.1995.1042.
Diesel exhaust (DE) is a known pulmonary carcinogen in rats, and the carcinogenic response is known to require the presence of soot. Many estimates of human lung cancer risk from inhaled DE have been developed from rat bioassay data or from the comparative mutagenic potencies of DE soot extract and known human chemical carcinogens. To explore the importance of the DE soot-associated organic compounds in the lung tumor response of rats, male and female F344 rats were exposed chronically to diluted whole DE or aerosolized carbon black (CB) 16 hr/day, 5 days/week at target particle concentrations of 2.5 mg/m3 (LDE, LCB) or 6.5 mg/m3 (HDE, HCB) or to filtered air. The CB served as a surrogate for the elemental carbon matrix of DE soot. Considering both the mass fraction of solvent-extractable matter and its mutagenicity in the Ames Salmonella assay, the mutagenicity in revertants per unit particle mass of the CB was three orders of magnitude less than that of the DE soot. Both DE soot and CB particles accumulated progressively in the lungs of exposed rats, but the rate of accumulation was higher for DE soot. In general, DE and CB caused similar, dose-related, nonneoplastic lesions. CB and DE caused significant, exposure concentration-related increases, of similar magnitudes, in the incidences and prevalences of the same types of malignant and benign lung neoplasms in female rats. The incidences of neoplasms were much lower in males than females, and the incidences were slightly higher among DE- than CB-exposed males. Survival was shortened in the CB-exposed males, and the shortened survival may have suppressed the expression of carcinogenicity as measured by crude incidence. Logistic regression modeling did not demonstrate significant differences between the carcinogenic potencies of CB and DE in either gender. The results suggest that the organic fraction of DE may not play an important role in the carcinogenicity of DE in rats.
柴油废气(DE)是大鼠已知的肺部致癌物,且已知致癌反应需要煤烟的存在。许多关于吸入DE导致人类肺癌风险的估计是根据大鼠生物测定数据或DE煤烟提取物与已知人类化学致癌物的比较致突变效力得出的。为了探究与DE煤烟相关的有机化合物在大鼠肺部肿瘤反应中的重要性,将雄性和雌性F344大鼠每天16小时、每周5天长期暴露于稀释的全DE或雾化炭黑(CB)中,目标颗粒浓度为2.5毫克/立方米(低剂量DE,低剂量CB)或6.5毫克/立方米(高剂量DE,高剂量CB),或暴露于过滤空气中。CB用作DE煤烟元素碳基质的替代物。考虑到溶剂可提取物的质量分数及其在艾姆斯沙门氏菌试验中的致突变性,CB每单位颗粒质量的回复突变体致突变性比DE煤烟低三个数量级。DE煤烟颗粒和CB颗粒在暴露大鼠的肺部都逐渐积累,但DE煤烟的积累速率更高。一般来说,DE和CB会引起相似的、剂量相关的非肿瘤性病变。CB和DE在雌性大鼠中导致相同类型的恶性和良性肺部肿瘤的发生率和患病率出现与暴露浓度相关的显著增加,且增加幅度相似。雄性大鼠的肿瘤发生率远低于雌性,且暴露于DE的雄性大鼠的发生率略高于暴露于CB的雄性大鼠。暴露于CB的雄性大鼠的生存期缩短,而生存期缩短可能抑制了以粗发病率衡量的致癌性表达。逻辑回归模型未显示CB和DE在任何性别中的致癌效力有显著差异。结果表明,DE的有机部分可能在大鼠DE致癌性中不起重要作用。