The role of trivalent dimethylated arsenic in dimethylarsinic acid-promoted skin and lung tumorigenesis in mice: tumor-promoting action through the induction of oxidative stress.
We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.
Mizoi
Mutsumi
M
Department of Environmental Toxicology and Carcinogenesis, Nihon University College of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
Takabayashi
Fumiyo
F
Nakano
Masayuki
M
An
Yan
Y
Sagesaka
Yuko
Y
Kato
Koichi
K
Okada
Shoji
S
Yamanaka
Kenzo
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000236:Adenoma / Q000139:chemically induced* / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D002101:Cacodylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006540:Herbicides / Q000378:metabolism / Q000633:toxicity*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism
D002273:Carcinogens; D006540:Herbicides; C472511:dimethylarsinous acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002101:Cacodylic Acid; D003849:Deoxyguanosine