Alterations of gene expression in skin and lung of mice exposed to light and cigarette smoke.
We previously showed that sunlight-mimicking light induces genotoxic damage not only in skin but also even in lung, bone marrow, and peripheral blood of hairless mice. Moreover, light and smoke acted synergically in the respiratory tract. To clarify the mechanisms involved, we investigated by cDNA-arrays the expression of 746 toxicologically relevant genes in skin and lungs of mice exposed for 28 days to light and/or environmental cigarette smoke. Glutathione-S-transferase-Pi and catalase were overexpressed in the lungs of mice exposed to light only. Moreover, the light induced in skin the expression of genes involved in carcinogenesis, photoaging, and production of genotoxic and oxidizing derivatives traveling at a distance. Smoke induced the expression of multiple genes in both skin and lung, which reflect adaptive responses and mechanisms related to cancer and, possibly, to emphysema and stroke. As shown in mice exposed to both light and smoke, the light tended to increase smoke-induced gene expression in lungs, while smoke tended to attenuate light-induced gene expression in skin. The oral administration of the nonsteroidal anti-inflammatory drug sulindac inhibited the light-induced overexpression of cyclooxygenase-2 and oxidative stress-related genes in skin, and down-regulated smoke-induced genes involved in oxidative stress, removal of damaged proteins, inflammation, and immune response in lung. These results provide a mechanistic insight explaining the systemic alterations induced by both light and smoke in mouse skin and lungs.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Genoa, Italy.
Cartiglia
Cristina
C
Longobardi
Mariagrazia
M
Balansky
Roumen M
RM
D'Agostini
Francesco
F
Lubet
Ronald A
RA
De Flora
Silvio
S
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D008027:Light; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D012906:Smoke / Q000009:adverse effects; D013467:Sulindac / Q000494:pharmacology; D014026:Nicotiana / Q000737:chemistry*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D012906:Smoke; D014028:Tobacco Smoke Pollution; D013467:Sulindac