Kuo E Y, Esber H J, Taylor D J, Bogden A E
Cancer Res. 1975 Aug;35(8):1975-80.
The effects of the following cancer chemotherapeutic agents on serum hormonal levels, estrous cycles, and endocrine organs were studied in mature, normal Sprague-Dawley rats by radioimmunoassay, vaginal smear examination, and organ weight end point: estradiol mustard (NSC 112259), testosterone mustard (NSC 112260), phenoestrin (NSC 104469), methotrexate (NSC 740), 5-fluorouracil (NSC 19893), vinblastine (NSC 49842), vincristine (NSC 67574), nitrogen mustard (NSC 762), and 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962). Following 2 weeks of treatment, estradiol-17beta levels were markedly elevated by all compounds except testosterone mustard and nitrogen mustard, which caused a decrease. Estrone levels were elevated by methotrexate, 5-fluorouracil, vinblastine, vincristine, nitrogen mustard, and 1,3-bis(2-chloroethyl)-1-nitrosourea, but were lowered by estradiol mustard. Progesterone levels were elevated only by estradiol mustard and testosterone mustard and were not affected by other compounds. Prolactin surge during proestrus was suppressed by phenesterin and methotrexate. Luteinizing hormone levels were lowered by methotrexate and nitrogen mustard. Estrous cycles of rats treated with estradiol mustard were arrested at proestrus, and the uterine and pituitary weights of these rats markedly increased. Uterine weight loss was significant following treatment with testosterone mustard, 5-fluorouracil, and nitrogen mustard. Thyroid weight was reduced by all compounds except methotrexate and vinblastine. Significant increases in pituitary weights occurred following treatment with all compounds except 1,3-bis(2-chloroethyl)-1-nitrosourea. The effects on ovarian and adrenal weights were minimal although significant by some compounds. Thus, in addition to their direct antitumor effects, these agents also produced changes in endocrine system which may be synergistic or antagonistic to the chemotherapy of endocrine-responsive neoplasms.
通过放射免疫测定、阴道涂片检查和器官重量终点法，研究了以下癌症化疗药物对成熟正常的斯普拉格-道利大鼠血清激素水平、发情周期和内分泌器官的影响：雌二醇氮芥（NSC 112259）、睾酮氮芥（NSC 112260）、苯雌酚（NSC 104469）、甲氨蝶呤（NSC 740）、5-氟尿嘧啶（NSC 19893）、长春碱（NSC 49842）、长春新碱（NSC 67574）、氮芥（NSC 762）和1,3-双（2-氯乙基）-1-亚硝基脲（NSC 409962）。治疗2周后，除睾酮氮芥和氮芥导致雌二醇-17β水平降低外，所有化合物均使其显著升高。甲氨蝶呤、5-氟尿嘧啶、长春碱、长春新碱、氮芥和1,3-双（2-氯乙基）-1-亚硝基脲使雌酮水平升高，但雌二醇氮芥使其降低。孕酮水平仅因雌二醇氮芥和睾酮氮芥而升高，不受其他化合物影响。苯雌酚和甲氨蝶呤抑制发情前期的催乳素激增。甲氨蝶呤和氮芥使促黄体生成素水平降低。用雌二醇氮芥治疗的大鼠发情周期停滞在发情前期，这些大鼠的子宫和垂体重量显著增加。用睾酮氮芥、5-氟尿嘧啶和氮芥治疗后子宫重量显著减轻。除甲氨蝶呤和长春碱外，所有化合物均使甲状腺重量减轻。除1,3-双（2-氯乙基）-1-亚硝基脲外，所有化合物治疗后垂体重量均显著增加。尽管某些化合物对卵巢和肾上腺重量有显著影响，但影响最小。因此，这些药物除了具有直接抗肿瘤作用外，还会引起内分泌系统的变化，这些变化可能与内分泌反应性肿瘤的化疗协同或拮抗。
