Lack of promoting effect due to oral administration of dimethylarsinic acid on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine.
Dimethylarsinic acid (DMA), a major metabolite of inorganic arsenics, and arsenic exposure is associated with tumor development in a wide variety of human tissues. In the present study, we examined whether DMA has tumor-promoting activity on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male, 8-week-old, F344 rats were treated with DHPN at a concentration of 0.1% in drinking water for 1 week, and starting 1 week thereafter, DMA was administered at concentrations of 0, 100, 200 or 400 ppm in the drinking water for 30 weeks. Induction of epithelial lesions, classified as alveolar epithelial hyperplasia, adenoma, and adenocarcinoma was evident in the lungs of DHPN-initiated animals, but no significant differences were found between DMA-treated groups and control groups. Furthermore, no significant differences in 5-bromo-2'-deoxyuridine labeling indices, as a marker of cell proliferation were observed among the groups. An additional group treated with DMA at concentrations of 200 ppm alone, without prior DHPN initiation was found to develop no epithelial lesions in the lung. There was no significant gain in 8-hydroxydeoxyguanosine formation, as a marker of oxidative stress, in the lungs of rats treated with DMA in their drinking water. In conclusion, oral-administered DMA does not exert promoting effects on rat lung carcinogenesis initiated with DHPN.
Seike
Noritaka
N
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, 545-8585, Osaka, Japan.
Wanibuchi
Hideki
H
Morimura
Keiichirou
K
Nishikawa
Takayuki
T
Kishida
Hideki
H
Nakae
Dai
D
Hirata
Kazuto
K
Fukushima
Shoji
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D009602:Nitrosamines / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D001152:Arsenicals; D002273:Carcinogens; D009153:Mutagens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine; C062856:dimethylarsine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine