Significance of chemical carcinogen-induced immunosuppression in mammary tumorigenesis in BALB-c mice.
Significance of chemical carcinogen-induced immunosuppression in mammary tumorigenesis in BALB-c mice.
复制标题
化学致癌物诱导的免疫抑制在 BALB-c 小鼠乳腺肿瘤发生中的意义。
作者：
D. Medina;G. Stockman;D. Griswold
本研究在BALB/c小鼠中研究了化学致癌物诱导的免疫抑制在致癌物诱导的乳腺肿瘤发生中的意义。在致癌物处理后1至100天之间测量用致癌剂量的3-甲基胆蒽（MCA）和7，12-二甲基苯并蒽处理的小鼠的免疫应答。通过皮肤和心脏同种移植物的排斥反应测定细胞介导的免疫，通过直接溶血素空斑试验测定体液免疫。MCA和7，12-二甲基苯并蒽抑制细胞介导的皮肤和心脏同种移植物的排斥反应长达50天后致癌剂治疗。致癌物处理小鼠的同种移植物存活时间比对照小鼠长50%至100%。在正常或致癌物处理的小鼠中，皮肤和心脏同种移植物的存活时间之间没有统计学显著差异。7，12-二甲基苯并蒽，但不是MCA，诱导了一个深刻的抑制原发性体液反应，持续长达100天后致癌物治疗。这种效应是菌株特异性的，因为MCA在C3 H中诱导了初次免疫应答的抑制，但在BALB/c小鼠中没有。最后，在涉及细胞介导的免疫和抵消体液阻断因子，即对甲基化牛血清白蛋白的超敏反应的测定系统中，MCA没有改变宿主的平衡免疫应答。为了直接回答致癌物诱导的免疫抑制是否是癌前乳腺组织中乳腺肿瘤发生的重要因素，将MCA处理的结节生长系D1的样品移植到已经用1.5 mg MCA处理的小鼠的乳腺游离脂肪垫中。这些副产物的肿瘤潜力与移植到未处理小鼠中的副产物相同，并且显著低于直接暴露于MCA的副产物。这些实验支持这样的论点，即致癌物诱导的免疫抑制和肿瘤发生之间没有简单的相关性，在乳腺肿瘤中产生的癌前副产物，MCA的免疫抑制功能不是必不可少的致癌功能。
Summary The significance of chemical carcinogen-induced immunosuppression in carcinogen-induced mammary tumorigenesis was investigated in BALB/c mice. The immune response of mice treated with a carcinogenic dose of 3-methylcholanthrene (MCA) and 7,12-dimethylbenzanthracene was measured between 1 and 100 days after carcinogen treatment. Cell-mediated immunity was measured by rejection of skin and heart homografts, and humoral immunity was measured by the direct hemolysin plaque assay. Both MCA and 7,12-dimethylbenzanthracene depressed cell-mediated rejection of skin and heart homografts for up to 50 days after carcinogen treatment. The survival time of homografts in carcinogen-treated mice was 50 to 100% greater than in control mice. There was no statistically significant difference between the survival times of skin and heart homografts in either normal or carcinogen-treated mice. 7,12-Dimethylbenzanthracene, but not MCA, induced a profound suppression of the primary humoral response which lasted up to 100 days after carcinogen treatment. This effect was strain specific since MCA induced suppression of the primary immune response in C3H but not in BALB/c mice. Finally, in an assay system that involves both cell-mediated immunity and a counteracting humoral blocking factor, namely, hypersensitivity to methylated bovine serum albumin, MCA did not alter the balanced immune response of the host. In an attempt to answer directly whether carcinogen-induced immune suppression was a significant factor in mammary tumorigenesis in preneoplastic mammary tissue, samples of MCA-treated nodule outgrowth line D1 were transplanted into the mammary gland free fat pads of mice already treated with 1.5 mg MCA. The tumor potential of these outgrowths was the same as outgrowths transplanted into untreated mice and significantly less than outgrowths exposed directly to MCA. These experiments support the contention that there is no simple correlation between carcinogen-induced immunosuppression and tumorigenesis in mammary tumors arising in preneoplastic outgrowths and that the immunosuppressive function of MCA is not essential for its carcinogenic function.