Less than additive interaction between cigarette smoke and chromium(VI) in inducing clastogenic damage in rodents
Less than additive interaction between cigarette smoke and chromium(VI) in inducing clastogenic damage in rodents
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DOI：
10.1093/carcin/21.9.1677
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发表时间：
2000-09-01
期刊：
影响因子：
4.7
通讯作者：
De Flora, S
中科院分区：
文献类型：
--
作者：
Balansky, RM;D'Agostini, F;De Flora, S
吸烟与某些物质的结合已被证明可以发挥协同致癌作用。另一方面，流行病学和实验数据也证明了烟雾和其他肺部致癌物之间的拮抗作用。尽管几十年来对接触六价铬的工人进行了大量研究，但吸烟习惯对这种金属诱发肺癌的影响尚未明确。因此，我们进行了两项研究，评估啮齿类动物的染色体断裂效应。在第一个实验中，BDF1 小鼠全身暴露于主流香烟烟雾中 5 天，并在最后一天接受腹膜内注射。注射重铬酸钾。在第二项研究中，Sprague-Dawley 大鼠连续 18 天全身暴露于环境香烟烟雾中，并在同一段时间内每天接受气管内滴注重铬酸钠。单独而言，两种六价铬盐和香烟烟雾，无论是主流烟雾还是环境烟雾，都会增加小鼠和大鼠骨髓多染红细胞中微核的频率。此外，个体暴露于环境香烟烟雾或重铬酸钠会增加大鼠肺泡巨噬细胞中微核和多核的频率。在这两项研究中，同时接触香烟烟雾和六价铬所产生的染色体断裂效应小于附加的断裂效应。这些结果与我们之前的数据一致，表明六价铬与苯并[a]芘或香烟烟雾冷凝物在体外致突变性测试系统中表现出拮抗作用，并且吸烟者的人肺泡巨噬细胞和外周肺实质的铬还原能力增强。总而言之，在没有任何流行病学证据的情况下，这些发现排除了香烟烟雾和六价铬之间存在任何协同作用，至少在致癌过程的某些阶段是如此。
A combination of tobacco smoking with certain agents has been shown to exert synergistic carcinogenic effects. On the other hand, antagonism betweeen smoke and other pulmonary carcinogens has also been documented by both epidemiological and experimental data. In spite of a very large number of studies carried out for decades in workers exposed to hexavalent chromium, the influence of smoking habits on lung carcinogenesis induced by this metal has not been clarified. For this reason, we performed two studies evaluating clastogenic effects in rodents. In the first one, BDF1 mice were exposed whole-body to mainstream cigarette smoke for 5 days and, on the last day, they received an i.p. injection of potassium dichromate. In the second study, Sprague-Dawley rats were exposed whole-body to environmental cigarette smoke for 18 consecutive days and for the same period of time they received daily intra-tracheal instillations of sodium dichromate. Individually, the two hexavalent chromium salts and cigarette smoke, either mainstream or environmental, enhanced the frequency of micronuclei in bone marrow polychromatic erythrocytes of both mice and rats. Moreover, individual exposure to either environmental cigarette smoke or sodium dichromate enhanced the frequency of micronuclei and multiple nuclei in pulmonary alveolar macrophages of rats. In both studies, combined exposure to cigarette smoke and hexavalent chromium produced less than additive clastogenic effects. These results are consistent with our previous data, showing that hexavalent chromium and either benzo[a]pyrene or cigarette smoke condensate behave antagonistically in in vitro mutagenicity test systems and that the chromium reducing capacity of human pulmonary alveolar macrophages and peripheral lung parenchyma is enhanced in smokers. Taken together, in the absence of any epidemiological evidence, these findings rule out any occurrence of synergism between cigarette smoke and hexavalent chromium, at least in certain stages of the carcinogenesis process.