Passive cigarette smoke exposure inhibits ultraviolet light B-induced skin tumors in SKH-1 hairless mice by blocking the nuclear factor kappa B signalling pathway.
Chronic exposure to sunlight [ultraviolet light B (UVB) irradiation] is the most common cause of non-melanoma skin tumors. In the present study, we investigated the effects of passive cigarette smoke superimposed over UVB irradiation, on tumor development, skin pathology and matrix changes in SKH-1 hairless mice. Groups of mice were exposed to 0.1 J/cm(2) of UVB five times per week for 20 weeks and/or exposure to passive cigarette smoke from 40 cigarettes a day over the same time period. UVB exposure resulted in an average of four large squamous cell carcinomas (SCC) and 15 smaller papillomas per mouse, whereas exposing the mice to both UVB + passive cigarette smoke completely prevented SCC formation and averaged less than one small papilloma per mouse. Oxidative DNA damage was investigated and there were no significant changes in the levels of urinary DNA adducts between control, smoke, UV and UV + smoke groups with the exception of 8-oxo guanine which was significantly reduced in the presence of passive cigarette smoke. Immunohistochemistry results revealed that tumor necrosis factor receptor 2 (TNF-R2), glycogen synthase kinase-3 beta, nuclear factor kappa B (NF-kappaB)/p65, KI-67 and cyclooxygenase 2 (COX-2) were markedly up-regulated in the epithelium by UVB exposure, whereas passive smoke exposure combined with the UVB irradiation completely blocked the expression of these proteins. Our results suggest that passive smoke exposure prevents UVB-induced SCC in mice and dramatically reduces the incidence of non-malignant papillomas by altering the NF-kappaB signalling pathway of tumorigenesis.
Gottipati
Koteswara R
KR
Department of Biochemistry, The University of Texas Health Science Center, Tyler, TX 76708, USA.
Poulsen
Henrik
H
Starcher
Barry
B
D000818:Animals; D004249:DNA Damage; D003877:Dermatitis, Contact / Q000209:etiology; D003895:Desmosine / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008812:Mice, Hairless; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010212:Papilloma / Q000209:etiology* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism; D014028:Tobacco Smoke Pollution; D014466:Ultraviolet Rays
D016328:NF-kappa B; D014028:Tobacco Smoke Pollution; D003895:Desmosine