Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1807–1815

Carbon monoxide signalling reduces photocarcinogenesis in the hairless mouse

Original Article

Abstract

Exposure of the skin of mice to UVA (320–400 nm) radiation has been shown to provide protection against the immunosuppressive effects of UVB (290–320 nm) radiation. The UVA protection was mediated via the UVA induction of the stress protein heme oxygenase-1, and its enzymatic product carbon monoxide (CO). Because UVB-induced immunosuppression is an accompanying and prerequisite feature of the promotion phase of photocarcinogenesis, the potential for immunoprotective CO to act as an anti-skin cancer agent was tested in this study. Groups of female albino Skh:hr-1 hairless mice were irradiated chronically with daily minimally erythemogenic doses of solar simulated UV radiation (SSUV) during a 10 week-period to induce photocarcinogenesis. The effect of repeated topical application of lotions containing a CO-releasing molecule (CORM-2; tricarbonyldichlororuthenium (II) dimer) at 250 or 500 μM, that had previously been shown in short-term experiments to provide photoimmune protection in mice, was measured. Tumor development was monitored for 29 weeks. Topical CORM-2 treatment was observed to reduce the acute and chronic inflammatory erythema reaction compared with control irradiated mice that did not receive CORM-2 lotions, and to reduce the chronic epidermal hyperplasia accompanying tumor outgrowth. The CORM-2 treatments provided a significant moderate inhibition of early tumor appearance dose-dependently, significantly reduced the average tumor multiplicity, increased the regression of established tumors dose-dependently, and inhibited the formation of large locally invasive tumors. The CORM-2 treatments also reduced the expression of immunosuppressive IL-10 in the uninvolved epidermis and dermis of tumor-bearing mice, and enhanced immunopotentiating epidermal IL-12 expression. Therefore CO signalling was revealed to have previously unrecognized anti-carcinogenic functions in the skin, consistent with a protective modulation of the epidermal cytokines. This is a novel observation that also implies that the UVA waveband that produces CO physiologically in exposed skin, might likewise be found to have an anti-photocarcinogenic action.

Keywords

Photocarcinogenesis Carbon monoxide Hairless mouse 

Abbreviations

CO

Carbon monoxide

CO-RM

Carbon monoxide-releasing molecule

CORM-2

Tricarbonyldichlororuthenium (II) dimer

DMSO

Dimethyl sulfoxide

HO-1

Heme oxygenase-1

PBS

Phosphate-buffered saline

SSUV

Solar simulated ultraviolet radiation

UVA

Ultraviolet A, 320–400 nm

UVB

Ultraviolet B, 290–320 nm

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Faculty of Veterinary ScienceUniversity of SydneySydneyAustralia

Personalised recommendations