Ishii Naomi, Gi Min, Fujioka Masaki, Yamano Shotaro, Okumura Mai, Kakehashi Anna, Wanibuchi Hideki
Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
J Toxicol Pathol. 2017 Jan;30(1):39-45. doi: 10.1293/tox.2016-0049. Epub 2016 Oct 23.
We have previously demonstrated that diphenylarsinic acid (DPAA) promotes liver carcinogenesis in rats in a medium-term liver carcinogenicity bioassay. However, the effects of DPAA on other organs have not been determined. In the present study, the effects of DPAA on carcinogenesis were investigated using a rat multiorgan carcinogenicity bioassay. A total of 60 six-week-old male F344 rats were treated with the carcinogens diethylnitrosamine, N-butyl-N-(4-hydroxybutyl) nitrosamine, N-methyl-N-nitrosourea, N-bis (2-hydroxypropyl) nitrosamine, and 1,2-dimethylhydrazine dihydrochloride to initiate carcinogenesis in multiple organs. After initiation, DPAA was given at a dose of 0, 5, or 20 ppm in drinking water for 27 weeks. The incidences of moderate and severe bile duct hyperplasia were significantly increased in the 20 ppm DPAA group (29.4%, 70.6%, respectively) compared with the 0 ppm DPAA group (0%, 0%, respectively), and the incidence and multiplicity of cholangioma were significantly increased in the 20 ppm DPAA group (29.4%, 0.4 ± 0.8/rat) compared with the 0 ppm DPAA group (0%, 0/rat). The total number and average area of glutathione S-transferase placenta form-positive foci, preneoplastic lesions in rat livers, were significantly increased in the 20 ppm DPAA group (10.5 ± 2.2/cm, 5.3 ± 1.7 mm/cm) compared with the 0 ppm DPAA group (6.2 ± 2.9/cm, 2.4 ± 1.4 mm/cm). In conclusion, our results demonstrate that DPAA promotes hepatobiliary carcinogenesis in a rat medium-term multiorgan carcinogenicity bioassay; no promotion effects were observed in other organs.
我们之前已经证明，在中期肝脏致癌性生物测定中，二苯基胂酸（DPAA）可促进大鼠肝脏致癌作用。然而，DPAA对其他器官的影响尚未确定。在本研究中，使用大鼠多器官致癌性生物测定来研究DPAA对致癌作用的影响。总共60只六周龄雄性F344大鼠用致癌物二乙基亚硝胺、N-丁基-N-（4-羟基丁基）亚硝胺、N-甲基-N-亚硝基脲、N-双（2-羟丙基）亚硝胺和二盐酸1,2-二甲基肼进行处理，以引发多个器官的致癌作用。启动后，以0、5或20 ppm的剂量在饮用水中给予DPAA，持续27周。与0 ppm DPAA组（分别为0%、0%）相比，20 ppm DPAA组中度和重度胆管增生的发生率显著增加（分别为29.4%、70.6%），并且与0 ppm DPAA组（0%、0/只大鼠）相比，20 ppm DPAA组胆管瘤的发生率和多发性显著增加（29.4%、0.4±0.8/只大鼠）。与0 ppm DPAA组（6.2±2.9/厘米、2.4±1.4毫米/厘米）相比，20 ppm DPAA组大鼠肝脏中谷胱甘肽S-转移酶胎盘形式阳性灶（癌前病变）的总数和平均面积显著增加（10.5±2.2/厘米、5.3±1.7毫米/厘米）。总之，我们的结果表明，在大鼠中期多器官致癌性生物测定中，DPAA可促进肝胆致癌作用；在其他器官中未观察到促进作用。
