Carcinogenicity of 2-hydroxybenzo(a)pyrene and 6-hydroxybenzo(a)pyrene in newborn mice.
Carcinogenicity of 2-hydroxybenzo(a)pyrene and 6-hydroxybenzo(a)pyrene in newborn mice.
复制标题
2-羟基苯并(a)芘和6-羟基苯并(a)芘对新生小鼠的致癌性。
作者：
R. Chang;P. Wislocki;J. Kapitulnik;A. Wood;W. Levin;H. Yagi;H. Mah;D. Jerina;A. Conney
用腹腔注射法检测苯并(A)芘(BP)、2-羟基苯并(A)芘(2-HOBP)和6-羟基苯并(A)芘(6-HOBP)的致瘤性。注射到新生小鼠体内。分别于生后第1、8、15天分别给予200、400、800nmoL的复方，24周龄处死。2-HOBP治疗引起的肺部肿瘤大约是BP的4倍，而6-HOBP几乎没有或几乎没有致瘤活性。用2-HOBP、BP和6-HOBP处理的新生小鼠的肺腺瘤发生率分别为98、81和11%，平均每只小鼠分别为24、6.4和0.11个腺瘤。对照组有7.5%的动物出现肺腺瘤，平均每只小鼠有0.08个腺瘤。当25、50或100nmolBP或2-HOBP每2周涂在小鼠皮肤上60周时，这两种化合物具有大致相同的致癌活性。这些结果证明了在一个以上的肿瘤系统中评估化学物质致癌潜力的重要性。在Aroclor 1254处理的大鼠肝微粒体存在下，测定了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。2-HOBP或BP在肝微体代谢过程中形成的产物具有明显的致突变活性。
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.