INHIBITION BY PHENOBARBITAL AND LACK OF EFFECT OF AMOBARBITAL ON THE DEVELOPMENT OF LIVER-TUMORS INDUCED BY N-NITROSODIETHYLAMINE IN JUVENILE B6C3F1 MICE

INHIBITION BY PHENOBARBITAL AND LACK OF EFFECT OF AMOBARBITAL ON THE DEVELOPMENT OF LIVER-TUMORS INDUCED BY N-NITROSODIETHYLAMINE IN JUVENILE B6C3F1 MICE
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DOI:
10.1016/0304-3835(84)90157-5
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发表时间:
1984-01-01
期刊:
影响因子:
9.7
通讯作者:
LYNCH, PH
LYNCH, PH
中科院分区:
医学1区
文献类型:
--
作者:
DIWAN, BA;RICE, JM;LYNCH, PH

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本文观察了苯巴比妥(PB)和异戊巴比妥(AB)对N-亚硝基二乙胺(DEN)诱发小鼠肝癌发生率的影响。在15日龄时用5 μ g DEN/g体重腹膜内注射40只B6 C3 F1雄性小鼠的组。从4周龄开始,DEN治疗组给予正常饮用水或含有0.05%PB或AB的水,持续36周。DEN单独诱导多个局灶性肝脏病变,包括肝细胞灶,肝细胞腺瘤和小梁癌。PB对DEN诱发的肝癌有抑制作用。在整个研究期间,暴露于PB的小鼠中的肝细胞病灶的大小(面积)显著更小,数量也更少。PB治疗延长了潜伏期或显着减缓了这些小鼠中肝细胞肿瘤的发展速度。在AB暴露的小鼠中没有观察到这种作用; AB既不抑制也不促进DEN预处理小鼠中局灶性肝损伤的发展。负责抑制DEN诱导的肝癌发生的可能机制包括PB的围产期给药的女性化效应。
The effects of phenobarbital (PB) and amobarbital (AB) on the rate of development of hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN) were studied in mice. Groups of 40 B6C3F1 male mice were injected i.p. at 15 days of age with 5 .mu.g DEN/g body wt. Beginning at 4 wk of age, DEN treated groups were given either normal drinking water or water containing either 0.05% PB or AB for up to 36 wk. DEN alone induced multiple focal hepatic lesions including hepatocellular foci, hepatocellular adenomas and trabecular carcinomas. Subsequent exposure to PB had a suppressing effect on DEN-induced hepatocarcinogenesis. Hepatocellular foci in PB-exposed mice were significantly smaller in size (area) and fewer in number throughout the study. PB treatment either prolonged the latency period or significantly slowed the rate at which hepatocellular tumors developed in these mice. No such effects were seen in AB-exposed mice; AB neither inhibited nor promoted the development of focal hepatic lesions in DEN-pretreated mice. Possible mechanisms responsible for the inhibition of DEN-induced hepatocarcinogenesis include the feminizing effects of perinatal administration of PB.