山梨医科大学雑誌 第9巻1号 027-035(1994)
<原著>去勢ラットを用いた前立腺発癌における
テストステロンのプロモーション作用の検討
白須宣彦,小松秀樹,上野 精
抄 録:F344系雄性ラットを用いて,プロモーション期にある前立腺に対して testosteroneの投与が前立腺癌の発生,進展に及ほす影響を検討した。11週齢で全ラットを去勢し,これをA〜Dの4群に分けた。去勢後3週間でA群,B群は testosterone propionate (TP) 25mg (平均体重227.5±21g)を3日間連続皮下投与して前立腺上皮の増殖を促し,1日おいてN-methyl-N-nitrosourea (MNU) 10mgを静脈内に投与した。さらにA群はMNU投与2日後より56週にわたり testosterone enanthate (TE) 12.5 mgを4週間に1度皮下に投与した。C群はTPおよびMNUは投与せず,A群と同期間TEを投与した。D群は去勢のみとした。60週で全群屠殺解剖し,病理組織学的に比較検討した。付属生殖器癌はA群では26匹中4匹(15%):前立腺癌3匹,精癌1匹に認めた。しかし,他の3群には付属生殖器癌は認めなかった。付属生殖器増殖性病変(癌+過形成)はA群では7/26(27%),C群では1/8(12%)に認めたが,B群,D群ではそれぞれ24匹,9匹のいずれにも認めなかった(A群,B群間にp<0.05で有意差あり)。プロモーション期のTE投与は付属生殖器増殖性病変に促進的に働くと思われた。またA,B両群には皮膚扁平上皮癌をそれぞれ16/26(62%),13/24(54%)にさらに小腸の腺癌をそれぞれ8/26(31%),4/24 (17%)に認めた。
キーワード ラットの前立腺癌,メチルニトロソウレア,テストステロン
Promoting Effects of Testosterone on Prostatic Carcinogenesis in Castrated F344 Rats
Nobuhiko Shirasu, Hideki Komatu, and Akira Ueno
The effect of exogenous testosterone in promoting prostatic carcinogenesis was examined using castrated F344 rats. All rats were castrated at 11 weeks of age and were divided into 4 groups. Rats in groups A and B were treated by 3 daily subcutaneous injections of 25 mg of testosterone propionate (TP) 3 weeks after the castration. Two days after the last TP injection, 10 mg of N-methyl-N-nitrosourea (MNU) was administered to each rat in these 2 groups. Two days after MNU treatment, testosterone enanthate (TE) administration was started in groups A and C. TE was injtcted subcutaneously at a dose of 12.5 mg for 56 weeks at intervals of 4 weeks. Rats in group D were control rats treated by castration only. All the rats were killed 60 weeks after the start of the experiment and examined histologically. Cancer in accessory sex organs was found only in group A at an incidence of 4/26 (15%); 3 prostatic cancer and 1 cancer of the seminal vesicle. Proliferative lesions (cancer+hyperplasia) of accessory sex organs developed in 7/26 (27%) in group A, 0/24 in group B, 1/8 (12%) in group C and 0/9 in group D (p<0.05 between group A and B). TE administration at the promotion stage appeared to increase the proliferative lesions in accessory sex organs. In groups A and B, squamous cell carcinoma of the skin was found at on incidence of 16/26 (62%) and 13/24 (54%), respectively, and adenocarcinoma of the small intestine at 8/26 (31%) and 4/24 (17%), respectively.
Key words: Prostatic cancer of rats, N-metyl-N-nitrosourea, Testosterone
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