Anderson C H, Hussain R A, Han M C, Beattie C W
Department of Anatomy and Cell Biology, University of Illinois, Chicago.
Cancer Lett. 1991 Jan;56(1):77-84. doi: 10.1016/0304-3835(91)90197-p.
Virgin 50-55-day-old rats exhibiting regular estrous cycles were injected i.v. with the direct acting carcinogen 1-nitroso-1-methylurea (NMU) on the morning of proestrus, estrus, or diestrus. Rats were killed at weekly intervals following NMU administration to identify source and number of microscopically identifiable dysplasias. Terminal end bud (TEB) abnormalities appeared within 1 week following NMU administration, with a significantly greater number of abnormal TEBs in mammary glands of rats injected on proestrus (PE) and estrus (E) than on diestrus (DE). Ductal (DH) and ductal alveolar hyperplasias (DAH) and hyperplastic alveolar nodules (HAN) appeared during week 3, with significantly more of each type of lesion appearing by 6 weeks after NMU injection. HAN were most numerous in glands from rats injected on estrus. Adenocarcinomas arose from both the proximal and distal ductal network; at 10 and 12 weeks post NMU, significantly more tumors were found in rats injected on proestrus than diestrus and estrus. These results support the theory that the hormonal environment at the time of NMU administration significantly alters early development of mammary tumors in the rat.
对处于规律发情周期的50 - 55日龄未孕大鼠，在动情前期、发情期或动情间期的早晨静脉注射直接作用的致癌物1-亚硝基-1-甲基脲（NMU）。在给予NMU后每周对大鼠进行处死，以确定显微镜下可识别的发育异常的来源和数量。在给予NMU后1周内出现终末芽（TEB）异常，与动情间期（DE）注射的大鼠相比，动情前期（PE）和发情期（E）注射的大鼠乳腺中异常TEB的数量显著更多。导管（DH）和导管腺泡增生（DAH）以及增生性肺泡结节（HAN）在第3周出现，在注射NMU后6周时每种病变类型出现的数量显著更多。HAN在发情期注射的大鼠腺体中最为常见。腺癌起源于近端和远端导管网络；在给予NMU后10周和12周，动情前期注射的大鼠中发现的肿瘤显著多于动情间期和发情期注射的大鼠。这些结果支持这样一种理论，即给予NMU时的激素环境会显著改变大鼠乳腺肿瘤的早期发展。
