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ORIGINAL ARTICLE Mice With Genetically Determined High Susceptibility to Ultraviolet (UV)-Induced Immunosuppression Show Enhanced UV Carcinogenesis.

Authors :
Noonan, Frances P.
Muller, H. Konrad
Fears, Thomas R.
Kusewitt, Donna F.
Johnson, Tracy M.
De Fabo, Edward C.
Source :
Journal of Investigative Dermatology. Nov2003, Vol. 121 Issue 5, p1175-1181. 7p.
Publication Year :
2003

Abstract

To assess the premise that genetically determined differences in susceptibility to UV-induced immunosuppression are reflected in UV carcinogenesis, we investigated UV skin cancer induction in two strains of reciprocal F1 hybrid mice CB6F1 males with high susceptibility to UV immunosuppression and a BALB/c X-chromosome and B6CF1 males with low susceptibility to UV immunosuppression and a C57BL/6 X-chromosome. Four experimental groups comprising both strains treated three times weekly with two UV regimens (daily doses incremented from 2.25 to 6 or 4.5 to 12 kJ per m2) were monitored for skin tumor development. Survival without a skin tumor differed over the four groups (p< 0.0001) and differed according to UV regimen within each strain (p<0.0005). Differences between strains were significant for the higher dose (p=0.03) but not for the lower dose (p=0.19) of UV, suggesting a dose–strain interaction. Comparing the higher UV dose regimen to the lower UV dose regimen within a strain at three reference points, tumor-free survival was reduced significantly more (p<0.05) in the CB6F1 mice than in the B6CF1 mice. Histologic assessment of all tumors revealed fibrosarcomas, squamous carcinomas, and mixed tumors. Immunohistochemistry of the mixed tumors for vimentin, keratin, and E-cadherin confirmed the presence of squamous and fibrosarcomatous elements. The enhanced susceptibility to UV carcinogenesis of CB6F1 males treated with the higher UV pro-tocol was attributable to a significantly enhanced proportion (p<0.005) of mixed tumors. Analysis of the data by comparing the proportion of animals tumor free at three reference time points confirmed a dose–strain interaction only in the development of mixed tumors, putatively the malignantly advanced carcinomas (p<0.03). A dose–strain interaction was also observed for systemic UV immunosuppression of contact hypersensitivity (p<0.025). These findings support the concept that genetic differences in susceptibility to UV-induced immunosuppression may be a risk factor for skin cancer. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022202X
Volume :
121
Issue :
5
Database :
Academic Search Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Academic Journal
Accession number :
11307140
Full Text :
https://doi.org/10.1046/j.1523-1747.2003.12560.x