Onami Saeko, Okubo Chigusa, Iwanaga Asuka, Suzuki Hiroaki, Iida Hajime, Motohashi Yurie, Tomonari Yuki, Otake Seiji, Tsuji Hiroyuki, Yoshimura Hiroyuki
Scientific Product Assessment Center, R and D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa 227-8512, Japan.
Pathology Department, Nonclinical Research Center, LSI Medience Corporation, 14-1 Sunayama, Kamisu, Ibaraki 314-0255, Japan.
J Toxicol Pathol. 2017 Jul;30(3):209-216. doi: 10.1293/tox.2017-0005. Epub 2017 Mar 31.
Some chemicals are known to be lung carcinogens in rodents. While many studies using two-stage models have administered medium or high doses to mice, few have tested lower doses. The dose dependence of urethane, 4-(-methyl--nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and benzo[a]pyrene (B[a]P), three well-known lung carcinogens at high doses, has not been sufficiently reported in lower dose ranges. Our study evaluated the tumorigenicity of urethane, NNK, and B[a]P at 26 weeks after a single intraperitoneal administration of each compound within medium to low dose in male and/or female A/JJmsSlc (A/J) mice. Dose-dependent tumorigenesis was demonstrated histopathologically for the three compounds. These results suggested that the tumorigenicity of these chemicals is dose dependent in A/J mice, even at lower doses than previously reported.
已知某些化学物质在啮齿动物中是肺部致癌物。虽然许多使用两阶段模型的研究对小鼠施用了中高剂量，但很少有研究测试较低剂量。在低剂量范围内，高剂量时三种著名的肺部致癌物——氨基甲酸乙酯、4-（-甲基- -亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）和苯并[a]芘（B[a]P）的剂量依赖性尚未得到充分报道。我们的研究评估了在雄性和/或雌性A/JJmsSlc（A/J）小鼠中，在中低剂量下单次腹腔注射每种化合物后26周时氨基甲酸乙酯、NNK和B[a]P的致瘤性。通过组织病理学证明了这三种化合物的剂量依赖性肿瘤发生。这些结果表明，即使在比先前报道更低的剂量下，这些化学物质在A/J小鼠中的致瘤性也是剂量依赖性的。
