Corr R, Berger M R, Betsch B, Floride J A, Brix H P, Schmähl D
Institute of Toxicology and Chemotherapy, German Cancer Research Centre, Heidelberg, FRG.
Br J Cancer. 1990 Jul;62(1):42-7. doi: 10.1038/bjc.1990.226.
This study concentrated on the influence of 2-chloroethylnitrosocarbamoyl-L-alanine (CNC-L-ala) linked to oestradiol (CNA-L-ala-E2) or dihydrotestosterone (CNC-L-ala-DHT) in position 17 of the respective steroid hormone on tumour growth and receptor kinetics of methylnitrosourea-induced rat mammary carcinoma. Both compounds almost completely arrested logarithmically growing mammary carcinoma of Sprague-Dawley rats: in the first week CNC-L-ala-E2 blocked the growth of these tumours by 92% compared to untreated control animals while, in animals treated with the physically equimolar mixture of CNC-L-ala and oestradiol (positive control), tumour growth was inhibited by 51% only. CNC-L-ala-DHT arrested the tumour growth in the first week by 95%, while the respective positive control (CNC-L-ala plus dihydrotestosterone) effected a growth inhibition of 71% compared to the untreated control. These results correlate well with the influence of both drugs on the cytosolic receptor content of sexual steroid hormones in the tumours. CNC-L-ala-E2 depleted the content of oestradiol receptors and kept it down for a week, while concomitantly the content of progesterone receptors increased considerably and that of androgen receptors showed a short-lived decrease. CNC-L-ala-DHT depleted androgen receptors as well as progesterone receptors. The content of androgen receptors remained low for a week, while that of progesterone receptors recovered within 8 days. The content of oestrogen receptors showed a moderate decrease.
本研究聚焦于与雌二醇（CNA-L-ala-E2）或二氢睾酮（CNC-L-ala-DHT）相连的2-氯乙基亚硝基氨基甲酰-L-丙氨酸（CNC-L-ala）在相应甾体激素17位上对甲基亚硝基脲诱导的大鼠乳腺癌肿瘤生长和受体动力学的影响。这两种化合物几乎完全抑制了斯普拉格-道利大鼠对数生长期的乳腺癌：在第一周，与未处理的对照动物相比，CNC-L-ala-E2使这些肿瘤的生长受到92%的抑制，而在用CNC-L-ala和雌二醇的物理等摩尔混合物处理的动物（阳性对照）中，肿瘤生长仅受到51%的抑制。CNC-L-ala-DHT在第一周使肿瘤生长受到95%的抑制，而相应的阳性对照（CNC-L-ala加二氢睾酮）与未处理的对照相比，生长抑制率为71%。这些结果与两种药物对肿瘤中性甾体激素胞质受体含量的影响密切相关。CNC-L-ala-E2耗尽了雌二醇受体的含量并使其在一周内保持较低水平，同时孕酮受体的含量显著增加，而雄激素受体的含量则短暂下降。CNC-L-ala-DHT耗尽了雄激素受体以及孕酮受体。雄激素受体的含量在一周内保持较低水平，而孕酮受体的含量在8天内恢复。雌激素受体含量出现适度下降。
