McNeill D A, Chrisp C E, Fisher G L
Battelle, Columbus, Ohio 43201.
Drug Chem Toxicol. 1990;13(1):71-86. doi: 10.3109/01480549009011070.
The pulmonary tumor response of Strain A mice has been reported to be a rapid and efficient predictor of carcinogenic potential for a variety of chemicals. The route of exposure has usually been by intraperitoneal injection (i.p.) of solubilized materials. We compared intratracheal (i.t.) instillation as a more representative route typical of human exposures, with i.p. injection of nickel subsulfide, a potent animal carcinogen. Animals were sacrificed either 20 weeks after the first dosing, or were held until 45 weeks after the first dosing. Urethane, a positive control, produced a significant increase in pulmonary tumor response after i.t. instillation as well as i.p. injection. For nickel subsulfide treated animals, there was no evidence of a dose-related increase in pulmonary tumor response in any i.p. or i.t. treatment group when compared with age-matched controls.
据报道,A品系小鼠的肺部肿瘤反应是多种化学物质致癌潜力的快速有效预测指标。通常的暴露途径是通过腹腔注射(i.p.)溶解的物质。我们将气管内(i.t.)滴注作为更具代表性的人类暴露典型途径,与腹腔注射硫化镍(一种强效动物致癌物)进行了比较。在首次给药后20周处死动物,或饲养至首次给药后45周。氨基甲酸乙酯作为阳性对照,在气管内滴注和腹腔注射后,肺部肿瘤反应均显著增加。对于硫化镍处理的动物,与年龄匹配的对照组相比,任何腹腔注射或气管内注射治疗组均无证据表明肺部肿瘤反应存在剂量相关增加。