Apoptotic Induction Mechanism of X-ray Irradiation Combined with Hydrogen Peroxide

Satoshi Fujita; Yoichiro Hosokawa; Ryo Saga; Eichi Tsuruga; Kazuhiko Okumura; Kentaro Ohuchi; Morio Ochi

doi:10.51083/radiatenvironmed.8.2_85

Regular Article

Apoptotic Induction Mechanism of X-ray Irradiation Combined with Hydrogen Peroxide

Satoshi Fujita, Yoichiro Hosokawa, Ryo Saga, Eichi Tsuruga, Kazuhiko Okumura, Kentaro Ohuchi, Morio Ochi

Author information

Satoshi Fujita
Hirosaki University Graduate School of Health Sciences, 66-1, Hon-cho, Hirosaki, Aomori 036-8564, Japan
Yoichiro Hosokawa
Hirosaki University Graduate School of Health Sciences, 66-1, Hon-cho, Hirosaki, Aomori 036-8564, Japan
Ryo Saga
Hirosaki University Graduate School of Health Sciences, 66-1, Hon-cho, Hirosaki, Aomori 036-8564, Japan
Eichi Tsuruga
Hirosaki University Graduate School of Health Sciences, 66-1, Hon-cho, Hirosaki, Aomori 036-8564, Japan
Kazuhiko Okumura
Division of Recostractive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan
Kentaro Ohuchi
Division of Recostractive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan
Morio Ochi
Division of Fixed Prosthodontics and Oral Implantology, Department of Oral Rehabilitation, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan

Keywords: radiation, hydrogen peroxide (H2O2), apoptosis, caspase, KORTUC (Kochi oxydol-radiation therapy for unresectable carcinomas)

JOURNAL FREE ACCESS

2019 Volume 8 Issue 2 Pages 85-93

DOI https://njjn-jsjc-gov-cn-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.51083/radiatenvironmed.8.2_85

Details

Abstract

Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC) is a clinical therapy, that combines X-ray irradiation and localized hydrogen peroxide. However few studies have reported the basic biological mechanism of action of KORTUC. Therefore we examined the effects of using a combination of hydrogen peroxide and X-ray irradiation on cell death. Cell viability of DU145, SAS, and HL60 cells decreased upon X-ray irradiation combined with exposure to hydrogen peroxide, compared to that on X-ray irradiation alone. DNA fragmentation of HL60 cells increased when cells were exposed to the combination treatment in comparison to X-ray irradiation, and apoptosis was considered to have increased. Abasic sites by DNA oxidative damage were observed early during X-ray irradiation, but no such increase was observed with hydrogen peroxide treatment. Caspase-3 and caspase-9 activities increased with all the three types of treatment, whereas caspase-8 showed high activity on treatment with hydrogen peroxide and the combination. The appearance of Bax and cytochrome c on X-ray irradiation and western blot analysis indicated the involvement of caspase-9 activation. Thus, cytochrome c was released via Bax, and the pathway leading directly from caspase-8 to caspase-3 was inferred to be induced with hydrogen peroxide treatment. The results suggested that hydrogen peroxide treatment induces apoptosis through a cascade that is different from that induced by irradiation, and combination with hydrogen peroxide is considered to enhance the effect of irradiation.

Corresponding author

Register with J-STAGE for free!