Effect of varying exposure regimens on methylene chloride-induced lung and liver tumors in female B6C3F1 mice.
Effect of varying exposure regimens on methylene chloride-induced lung and liver tumors in female B6C3F1 mice.
复制标题
不同暴露方案对雌性 B6C3F1 小鼠二氯甲烷诱导的肺和肝肿瘤的影响。
作者：
Frank Kari;Julie F. Foley;S. Seilkop;R. Maronpot;M. Anderson
二氯甲烷是一种高产化学品，用于各种应用，估计每天至少有100万人在职业和消费者接触。先前报告的吸入二氯甲烷的慢性评价结果表明，它导致Fischer 344大鼠的乳腺肿瘤和B6 C3 F1小鼠的肺和肝肿瘤。二氯甲烷诱导的致癌机制尚未得到充分阐明。在本文中，我们描述了动物的组织学评价，在一些间歇时间的目的，评估肝脏和肺肿瘤的进展。此外，还进行了一系列停止暴露处理，以评价不同二氯甲烷暴露持续时间对雌性小鼠肝脏和肺部肿瘤诱导的作用。吸入暴露于2000 ppm二氯甲烷，每天6小时，每周5天，持续104周，导致暴露动物肺腺瘤或癌的发生率增加8倍（63对7.5%; P < 0.01），每只风险动物的肺腺瘤和癌总数增加了13倍（0.97对0.075; P < 0.01）。这种暴露还导致小鼠肝肿瘤发生率增加2.5倍（69对27%; P < 0.01），每只风险动物的肝腺瘤和癌总数增加3倍（1.34对0.46; P < 0.01）。与对照动物相比，二氯甲烷暴露加速了肺肿瘤的首次出现（1年）;化学诱导和自发性肝肿瘤首次同时发生。较短的暴露持续时间足以获得最大数量的肺肿瘤比所需的最大肝肿瘤负荷。停止化学治疗后延长时间，肺肿瘤多样性显著增加。这与肝脏中的结果形成对比，与停止暴露后立即评价的小鼠相比，额外的暴露后潜伏时间不会影响肿瘤多样性。暴露于二氯甲烷的动物中肺泡增生的发生率非常低，即使在荷瘤动物中也是如此，并且直到腺瘤和癌出现后至少13周才观察到增生。因此，B6 C3 F1小鼠中二氯甲烷诱导的肺肿瘤的发生之前没有明显的细胞毒性、增强的细胞增殖或观察到的增生。（400字处截断摘要）
Methylene chloride is a high production chemical used in a variety of applications resulting in estimated occupational and consumer exposures of at least one million people per day. Results of previously reported chronic evaluations of inhaled methylene chloride indicated that it caused mammary tumors in Fischer 344 rats and neoplasia in the lungs and liver of B6C3F1 mice. Mechanism(s) for methylene chloride-induced carcinogenesis have not been adequately elucidated. In this paper we describe the histologic evaluation of animals at a number of intermittent times for the purposes of assessing the progressive development of liver and lung neoplasia. Additionally, a series of stop-exposure treatments was conducted to evaluate the role of different methylene chloride exposure durations on the induction of hepatic and pulmonary neoplasia in female mice. Inhalation exposure to 2000 p.p.m. methylene chloride for 6 h per day, 5 days per week, for 104 weeks resulted in an 8-fold increase in the incidence of exposed animals having a lung adenoma or carcinoma (63 versus 7.5%; P < 0.01) and a 13-fold increase in the total number of pulmonary adenomas and carcinomas per animal at risk (0.97 versus 0.075; P < 0.01). This exposure also caused a 2.5-fold increase in the incidence of mice having liver tumors (69 versus 27%; P < 0.01) and a 3-fold increase in the total number of hepatic adenomas and carcinomas per animal at risk (1.34 versus 0.46; P < 0.01). Methylene chloride exposure hastened the first appearance of lung tumors (by 1 year) compared to that observed in control animals; chemical-induced and spontaneous liver tumors first occurred simultaneously. A shorter exposure duration was sufficient to attain maximal numbers of lung tumors than that needed for a maximal liver tumor burden. Lung tumor multiplicity was substantially increased by having additional time after cessation of the chemical treatment. This contrasts with the findings in liver, where additional post-exposure latency time did not effect tumor multiplicity compared to that of mice evaluated immediately after cessation of exposure. The incidence of lung alveolar hyperplasia in methylene chloride exposed animals was very low, even in tumor-bearing animals and the hyperplasias were not seen until at least 13 weeks after appearance of adenomas and carcinomas. Thus, the genesis of methylene chloride induced lung tumors in B6C3F1 mice is not preceded by overt cytotoxicity, enhanced cell proliferation nor observed hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS)