Oral administration of dimethylarsinic acid, a main metabolite of inorganic arsenic, in mice promotes skin tumorigenesis initiated by dimethylbenz(a)anthracene with or without ultraviolet B as a promoter.
Concerning arsenic-induced tumorigenesis, an animal model must be developed for understanding the mechanism of human carcinogenesis by arsenics. To determine whether orally administered dimethylarsinic acid (DMA) promotes and causes the progression of skin tumorigenesis, an animal protocol by topical application of dimethylbenz(a)anthracene (DMBA) with or without UVB, a tumor promoter, in hairless mice was used. The administration of DMA by the oral route promoted not only the formation of papillomas induced by DMBA alone but also the formation of malignant tumors induced by way of the formation of atypical keratoses by treatment with DMBA and UVB. A phenomenon, the progression of keratoses-->atypical keratoses-->squamous cell carcinomas (SCCs), observed in the present study may resemble the development of tumors in arsenic-exposed humans. We also discussed the involvement of a reactive oxygen species (ROS), e.g., the dimethylarsenic peroxy radical [(CH3)2AsOO.], produced during the metabolic processing of DMA, in skin and in multi-organ tumorigenesis.
Yamanaka
K
K
College of Pharmacy, Nihon University, Funabashi, Chiba, Japan. yamanaka@pha.nihon-u.ac.jp
Mizol
M
M
Kato
K
K
Hasegawa
A
A
Nakano
M
M
Okada
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015127:9,10-Dimethyl-1,2-benzanthracene; D000284:Administration, Oral; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D003043:Cocarcinogenesis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009153:Mutagens / Q000633:toxicity*; D017382:Reactive Oxygen Species; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014466:Ultraviolet Rays
D001152:Arsenicals; D009153:Mutagens; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; C062856:dimethylarsine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine