Stevens R H, Cole D A
Environ Res. 1983 Oct;32(1):25-36. doi: 10.1016/0013-9351(83)90188-3.
This study was initiated to investigate the possible perinatal carcinogenic effects of the colon carcinogen 1,2-dimethylhydrazine (DMH) in Fischer F344 inbred rats. Pregnant female animals during their 16-18th day of gestation were administered the chemical by intraperitoneal injections, and beginning at 4 months postparturition, the antitumor cell-mediated immunity (CMI) was delineated in the dams and pups as an indirect measure of carcinogenesis. The CMI status was established by the ability of peripheral blood lymphoid cells obtained from the rats to injure and kill target tumor cells derived from an X-ray-induced rat small bowel adenocarcinoma cell line with the degree of damage being reflected in the quantity of loss of radioiodinated peripheral and integral membrane proteins from the target cells. A significant antitumor CMI was observed in the exposed offsprings although there was no apparent difference between the immunoresponsiveness observed in either the males or the female siblings. Unexpectedly, the mothers exhibited little such antitumor cellular immunity following the carcinogenic insult; even though all previous investigations of adult animals always demonstrated such an immunological response following exposure to the quantities of DMH that were administered (0.1 to 20 mg per kg body wt). As a consequence, these findings tentatively implied that the state of pregnancy alters a female's response to chemical carcinogenic insults and may actually serve as a device for protection from environmentally caused cancer. The threshold detection level for DMH exposure utilizing immune measurements was found to be approximately 10 times smaller for the perinatal susceptibility to the chemical insult intimating that such tests might usefully be incorporated in those bioassays utilized for determining the cancer-causing potential of weak carcinogens. Our findings now suggest that DMH may indeed be a perinatal carcinogen and that immune responsiveness may be readily employed for identifying such substances. However, the definitive studies of actually identifying cancer following such in utero exposures remain to be accomplished.
本研究旨在探讨结肠致癌物1,2 - 二甲基肼（DMH）对Fischer F344近交系大鼠可能产生的围产期致癌作用。在妊娠第16 - 18天的孕鼠通过腹腔注射给予该化学物质，产后4个月开始，在母鼠和幼崽中检测抗肿瘤细胞介导免疫（CMI），以此作为致癌作用的间接指标。通过从大鼠获取的外周血淋巴细胞损伤和杀死源自X射线诱导的大鼠小肠腺癌细胞系的靶肿瘤细胞的能力来确定CMI状态，损伤程度通过靶细胞放射性碘化外周膜蛋白和整合膜蛋白的损失量来反映。在暴露的后代中观察到显著的抗肿瘤CMI，尽管在雄性或雌性同胞中观察到的免疫反应性没有明显差异。出乎意料的是，母亲在致癌损伤后几乎没有表现出这种抗肿瘤细胞免疫；尽管之前对成年动物的所有研究总是表明，在暴露于所给予剂量（每千克体重0.1至20毫克）的DMH后会出现这种免疫反应。因此，这些发现初步表明，妊娠状态会改变雌性对化学致癌损伤的反应，实际上可能起到预防环境致癌的作用。利用免疫测量法检测DMH暴露的阈值水平发现，围产期对化学损伤的易感性约为其10倍，这表明此类检测可能有助于纳入用于确定弱致癌物致癌潜力的生物测定中。我们的研究结果现在表明，DMH可能确实是一种围产期致癌物，免疫反应性可用于识别此类物质。然而，关于子宫内暴露后实际鉴定癌症的确定性研究仍有待完成。
