Steffensen I L, Paulsen J E, Engeset D, Kronberg L, Alexander J
National Institute of Public Health, Department of Environmental Medicine, Oslo.
Pharmacol Toxicol. 1999 Aug;85(2):56-64. doi: 10.1111/j.1600-0773.1999.tb00067.x.
Epidemiological studies indicate an association between exposure to chlorinated drinking water and risk of intestinal cancer. In order to study this experimentally, we have examined the effects of 3,4-dichloro-5-hydroxy-2[5H]-furanone (mucochloric acid, MCA) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), mutagenic and genotoxic compounds in drinking water, on aberrant crypt foci and tumours in the intestines of male F344 rats and Balb/cA mice, and C57BL/6J-Min (multiple intestinal neoplasia)/+ mice of both sexes, in six independent experiments. In some experiments the effects of MCA and MX on aberrant crypt foci induced by the colon carcinogens 1,2-dimethylhydrazine or its metabolite azoxymethane were also studied. Neither MCA nor MX alone induced aberrant crypt foci or intestinal tumours when given in drinking water. With this route of exposure neither MCA nor MX, when given in combination with 1,2-dimethylhydrazine or azoxymethane, had any effect on the induction or growth of the aberrant crypt foci. Drinking water exposure of MX did not affect the number or growth of aberrant crypt foci or intestinal tumours in the Minl+ mice. When administered intrarectally MCA had a weak inducing effect on aberrant crypt foci in the colons of Balb/cA mice. Exposure to MCA and MX intrarectally apparently promoted the growth of aberrant crypt foci both in rats and mice, increasing the crypt multiplicity, aberrant crypts/aberrant crypt foci. Based on an overall evaluation of these experiments, the intestinal tract, at least in rats and mice, seems not to be a main target organ for effects of MCA or MX on preneoplastic or neoplastic development.
流行病学研究表明，饮用氯化水与患肠癌风险之间存在关联。为了对此进行实验研究，我们在六项独立实验中，检测了饮用水中具有致突变性和基因毒性的化合物3,4 - 二氯 - 5 - 羟基 - 2[5H] - 呋喃酮（粘氯酸，MCA）和3 - 氯 - 4 -（二氯甲基）- 5 - 羟基 - 2[5H] - 呋喃酮（MX）对雄性F344大鼠、Balb/cA小鼠以及两性C57BL/6J - Min（多发性肠道肿瘤）/+小鼠肠道中异常隐窝灶和肿瘤的影响。在一些实验中，还研究了MCA和MX对由结肠致癌物1,2 - 二甲基肼或其代谢产物偶氮甲烷诱导产生的异常隐窝灶的影响。当通过饮水给予时，MCA和MX单独使用均未诱导出异常隐窝灶或肠道肿瘤。通过这种暴露途径，当MCA和MX与1,2 - 二甲基肼或偶氮甲烷联合使用时，对异常隐窝灶的诱导或生长均无任何影响。饮用含MX的水对Min/+小鼠中异常隐窝灶的数量或生长没有影响。当经直肠给予时，MCA对Balb/cA小鼠结肠中的异常隐窝灶有微弱的诱导作用。经直肠暴露于MCA和MX显然促进了大鼠和小鼠中异常隐窝灶的生长，增加了隐窝多样性，即异常隐窝/异常隐窝灶。基于对这些实验的全面评估，至少在大鼠和小鼠中，肠道似乎不是MCA或MX对肿瘤前或肿瘤发展产生影响的主要靶器官。
