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2-羟基苯并(a)芘和6-羟基苯并(a)芘对新生小鼠的致癌性。

Carcinogenicity of 2-hydroxybenzo(a)pyrene and 6-hydroxybenzo(a)pyrene in newborn mice.

作者信息

Chang R L, Wislocki P G, Kapitulnik J, Wood A W, Levin W, Yagi H, Mah H D, Jerina D M, Conney A H

出版信息

Cancer Res. 1979 Jul;39(7 Pt 1):2660-4.

PMID:376121
Abstract

Benzo(a)pyrene (BP), 2-hydroxybenzo(a)pyrene (2-HOBP), and 6-hydroxybenzo(a)pyrene (6-HOBP) were tested for tumorigenicity by i.p. injection into newborn mice. The mice were treated sequentially with 200, 400, and 800 nmol of compound on the first, eighth and fifteenth day of life, and the animals were killed at 24 weeks of age. Treatment with 2-HOBP caused about 4-fold more pulmonary tumors than BP, while 6-HOBP had little or no tumorigenic activity. Newborn mice treated with 2-HOBP, BP, and 6-HOBP had a 98, 81, and 11% incidence of pulmonary adenomas with an average of 24, 6.4, and 0.11 adenomas per mouse, respectively. In the control group, 7.5% of the animals had pulmonary adenomas with an average of 0.08 adenoma per mouse. When 25, 50, or 100 nmol of BP or 2-HOBP was applied to mouse skin once every 2 weeks for 60 weeks, both compounds had about the same carcinogenic activity. These results demonstrate the importance of evaluating the carcinogenic potential of chemicals in more than one tumor system. BP and 2-HOBP were tested for mutagenicity towards two strains of Salmonella typhimurium and towards Chinese hamster V79 cells in the presence of hepatic microsomes from rats pretreated with Aroclor 1254. The products formed during the metabolism of 2-HOBP or BP by liver microsomes had significant mutagenic activity.

摘要

通过腹腔注射将苯并(a)芘(BP)、2-羟基苯并(a)芘(2-HOBP)和6-羟基苯并(a)芘(6-HOBP)注射到新生小鼠体内,以测试其致癌性。在小鼠出生后的第1天、第8天和第15天,依次用200、400和800 nmol的化合物进行处理,动物在24周龄时处死。用2-HOBP处理导致的肺肿瘤数量比BP多约4倍,而6-HOBP几乎没有致癌活性。用2-HOBP、BP和6-HOBP处理的新生小鼠肺腺瘤的发生率分别为98%、81%和11%,平均每只小鼠分别有24个、6.4个和0.11个腺瘤。在对照组中,7.5%的动物有肺腺瘤,平均每只小鼠有0.08个腺瘤。当每2周将25、50或100 nmol的BP或2-HOBP应用于小鼠皮肤,持续60周时,这两种化合物具有大致相同的致癌活性。这些结果证明了在多个肿瘤系统中评估化学物质致癌潜力的重要性。在存在用多氯联苯1254预处理的大鼠肝微粒体的情况下,对BP和2-HOBP对两株鼠伤寒沙门氏菌和中国仓鼠V79细胞的致突变性进行了测试。肝微粒体在代谢2-HOBP或BP过程中形成的产物具有显著的致突变活性。

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