Suzuki Hiroshi, Ikeda Naohiro, Kobayashi Kazuo, Terashima Yukari, Shimada Yasushi, Suzuki Takayoshi, Hagiwara Toshiyuki, Hatakeyama Shigeki, Nagaoka Koko, Yoshida Junichi, Saito Yukiko, Tanaka Jin, Hayashi Makoto
Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano 399-4501, Japan.
Mutat Res. 2005 Jun 6;583(2):133-45. doi: 10.1016/j.mrgentox.2005.03.012.
We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual.
我们对幼鼠进行了肝脏和外周血微核试验,使用了七种啮齿动物肝癌致癌物——4,4'-亚甲基二苯胺(MDA)、喹啉、邻甲苯胺、4-氯邻苯二胺(CPDA)、二甲基亚硝胺(DMN)、对二甲基氨基偶氮苯(DAB)和邻苯二甲酸二(2-乙基己基)酯(DEHP)——以及两种诱变化学物质——曲酸和甲磺酸甲酯(MMS)。喹啉、DMN和DAB在肝脏试验中呈阳性,而邻甲苯胺、曲酸、DAB和MMS在外周血试验中呈阳性。据报道,邻甲苯胺、曲酸和DAB在小鼠骨髓微核试验中呈阴性,表明存在种属差异。我们的结果揭示了肝细胞微核诱导与肝癌致癌性之间的相关性。该技术可用于检测需要代谢活化的微核诱导化学物质,并且能够同时比较同一动物个体肝脏和外周血中化学物质的微核诱导潜力。