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A-4.5.2 The Combined Effect of Ultraviolet Irradiation and Toxic Chemicals on the Skin Tumorigenesis: Role of Oxidative Stress

[Contact Person]

Chiharu Tohyama, Ph.D.
Environmental Health Sciences Division
National Instiute for Environmental Studies
16-2 Onogawa, Tsukuba, Ibaraki 305-0053, Japan
Tel: 0298-50-2336
Fax: 0298-50-2574
E-mail:ctohyama@nies.go.jp

Total Budget for FY 1996-1998;

6,000,000 Yen (FY 1998; 2,000,000 Yen)

Abstract

Based upon the earlier findings that UV as well as quite a few carcinogens exert their harmful effects through oxidative stress, we focus upon the oxidative stress and skin cancers in our study. We have used metallothionein knock out [MT (-/-)] mice that are susceptible to oxidative damage, and had them exposed to UVB irradiation and 7,12-dimethylbenz[a] anthracene (DMBA), a well-known carcinogen. The acute exposure to UVB showed that UVB (5 KJ/m²) induced same skin thickness response in both strains of mice. DMBA induced strong acute inflammatory responses in the skin of MT (-/-) mice than wild type [MT (+/+)] mice. The skin damage was more serious after short time of combined exposure. Moreover, Topical application of administration of DMBA resulted in an increase in papilloma in MT (-/-) mice skin in a dose-dependent manner after 14 weeks of treatment. However, no change was observed in the skin of MT (+/+) mice by DMBA treatment. The long-term UVB irradiation enhanced the skin tumor incidence caused by DMBA. These results suggested MT plays a defensive role against skin tumorigenesis of DMBA and UVB. The experimental result obtained so far provides that genetic traits on sensitivity to oxidative stress should be thought for the health risk assessment of human populations. Ultraviolet irradiation, 7,12-Dimethylbenz[a] anthracene,

[Key Words]

Skin carcinogenesis, Oxidative stress, Metallothionein.