title: Diphenylarsinic acid exerts promotion effects on hepatobiliary carcinogenesis in a rat medium-term multiorgan carcinogenicity bioassay.
abstract: 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/cm2, 5.3 ± 1.7 mm2/cm2) compared with the 0 ppm DPAA group (6.2 ± 2.9/cm2, 2.4 ± 1.4 mm2/cm2). 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.
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Gi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujioka
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
keywords: DMBDD; bile duct hyperplasia; cholangioma; diphenylarsinic acid; liver carcinogenesis