EFFECT OF CARCINOGEN DOSE AND AGE AT ADMINISTRATION ON INDUCTION OF MAMMARY CARCINOGENESIS BY 1-METHYL-1-NITROSOUREA
EFFECT OF CARCINOGEN DOSE AND AGE AT ADMINISTRATION ON INDUCTION OF MAMMARY CARCINOGENESIS BY 1-METHYL-1-NITROSOUREA
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DOI：
10.1093/carcin/13.9.1535
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发表时间：
1992-09-01
期刊：
影响因子：
4.7
通讯作者：
SINGH, M
中科院分区：
文献类型：
--
作者：
THOMPSON, HJ;ADLAKHA, H;SINGH, M
本文报告的工作的目的是确定是否致瘤反应1-甲基-1-亚硝基脲（MNU）在乳腺不同的年龄管理和剂量依赖性时，注射致癌剂之前50天的年龄。使用最近开发的乳腺肿瘤诱导方法，在35日龄时以25至75 mg/kg或在28、35或42日龄时以50 mg/kg的剂量腹膜内注射MNU。用MNU治疗导致良性和恶性乳腺肿瘤的诱导。在50 mg/kg剂量及以上的MNU剂量下，乳腺腺癌的发生率为100%，与给予致癌物的年龄无关。癌症的数量与致癌物剂量成比例地增加，而癌症潜伏期随着MNU剂量的增加而减少。在28、35或42日龄注射50 mg MNU/kg体重的大鼠中，各组之间的癌症发病率、数量或潜伏期差异无统计学意义。在35或42日龄注射MNU的大鼠中观察到乳腺肿瘤向肺、肝和脾的转移。这些数据表明：（i）在50日龄之前开始的大鼠中，MNU诱导的乳腺癌发生的剂量反应性;（ii）如果在50日龄之前，则开始时的年龄对最终肿瘤结局没有影响;（iii）注射MNU的年龄可能影响诱导的乳腺癌的转移潜力。
The objective of the work reported in this paper was to determine if the tumorigenic response to 1-methyl-1-nitrosourea (MNU) in the mammary gland varied with age of administration and was dose dependent when the carcinogen was injected prior to 50 days of age. Using a recently developed method for mammary tumor induction, MNU was injected i.p. at doses ranging from 25 to 75 mg/kg at 35 days of age or 50 mg/kg at 28, 35 or 42 days of age. Treatment with MNU resulted in induction of both benign and malignant mammary tumors. The incidence of mammary gland adenocarcinomas was 100% at and above the 50 mg/kg dose of MNU, irrespective of the age at which carcinogen was administered. The number of cancers increased in proportion to carcinogen dose, whereas cancer latency decreased as the MNU dose increased. In rats injected with 50 mg MNU/kg body weight at 28, 35 or 42 days of age, differences among groups in cancer incidence, number or latency were not statistically significant. Metastases of mammary neoplasms to lung, liver and spleen were observed in rats injected with MNU at 35 or 42 days of age. These data indicate (i) the dose responsiveness of MNU-induced mammary carcinogenesis in rats initiated prior to 50 days of age; (ii) the lack of effect of age at initiation if prior to 50 days on final tumor outcome; and (iii) that the age at which MNU is injected may affect the metastatic potential of the mammary carcinomas that are induced.