Geter David R, George Michael H, Moore Tanya M, Kilburn Steve, Huggins-Clark Gloria, DeAngelo Anthony B
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
J Toxicol Environ Health A. 2004 Jan 9;67(1):23-9. doi: 10.1080/15287390490253642.
Bromodichloromethane (BDCM) and tribromomethane given by corn oil gavage were previously found to induce neoplasia in the large intestine of rats. Our chronic bioassay of BDCM administered in drinking water failed to produce colon neoplasia in male F344/N rats. We recently reported that BDCM induces aberrant crypt foci (ACF), putative precursor lesions in the development of colon cancer, when included in the drinking water of male rats. To investigate whether ACF induced by BDCM could be promoted by corn oil (CO), male F344/N rats were exposed to 0.7 g BDCM/L in drinking water or 50 mg BDCM/kg body weight by oral gavage in CO. Animals exposed to drinking water, CO, or 15 mg/kg azoxymethane (AOM) (ip) constituted the negative, vehicle, and positive controls. After 26 wk, colons were examined for ACF. A significant decrease in water consumption was observed in both the positive controls and BDCM-treated animals; however, no difference was noted in final body weight. The administration of CO to AOM-exposed animals produced a significant increase in total ACF when compared to AOM alone. BDCM produced a significant increase in ACF when compared to control, but no difference was noticed between BDCM exposure by oral CO gavage and control. Additionally, no difference was noted between BDCM exposure by drinking water and by oral CO gavage. This study demonstrates that the formation of ACF is independent of the route of BDCM exposure (drinking water vs. oral corn oil gavage), with both routes producing similar ACF values of 1.33 +/- 0.49 and 1.5 +/- 0.51 ACF/colon.
先前发现,经玉米油灌胃给予的溴二氯甲烷(BDCM)和三溴甲烷可诱发大鼠大肠肿瘤。我们对饮水中给予BDCM的慢性生物测定未能在雄性F344/N大鼠中诱发结肠肿瘤。我们最近报告称,当BDCM包含在雄性大鼠的饮水中时,它会诱发异常隐窝灶(ACF),这是结肠癌发展过程中的假定前体病变。为了研究BDCM诱导的ACF是否可被玉米油(CO)促进,将雄性F344/N大鼠暴露于饮水中0.7 g BDCM/L或经口灌胃给予50 mg BDCM/kg体重(溶于CO中)。暴露于饮用水、CO或15 mg/kg氧化偶氮甲烷(AOM)(腹腔注射)的动物分别构成阴性对照、赋形剂对照和阳性对照。26周后,检查结肠中的ACF。在阳性对照和BDCM处理的动物中均观察到饮水量显著下降;然而,最终体重未发现差异。与单独给予AOM相比,给暴露于AOM的动物给予CO后,总ACF显著增加。与对照相比,BDCM使ACF显著增加,但经口CO灌胃暴露BDCM与对照之间未发现差异。此外,饮水中暴露BDCM与经口CO灌胃暴露BDCM之间也未发现差异。本研究表明,ACF的形成与BDCM的暴露途径(饮水与经口玉米油灌胃)无关,两种途径产生的ACF值相似,分别为1.33±0.49和1.5±0.51个ACF/结肠。