Carcinogenesis Advance Access published online on July 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgg108
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Health Sciences, University of Genoa, via A. Pastore 1, I-16132 Genoa, Italy; National Centre of Oncology, Sofia-1756, Bulgaria
* Corresponding author. E-mail: sdf{at}unige.it.
Received 29 April 2003
; revised 16 June 2003
; accepted 17 June 2003
No information is available on the interaction between cigarette smoke, the most important man-made carcinogen, and light, the most widespread natural carcinogen. In order to clarify this issue, SKH-1 hairless mice were exposed to environmental smoke and/or to the light emitted by sunlight-simulating halogen quartz bulbs. After 28 days, intermediate biomarkers were evaluated in skin, respiratory tract, bone marrow, and peripheral blood. The results showed that, individually, the light produced extensive alterations not only in the skin but even at a systemic level, as shown by formation of bulky DNA adducts in both lung and bone marrow and induction of cytogenetic damage in bone marrow and peripheral blood erythrocytes. Smoke damaged the respiratory tract and produced significant alterations in the skin as well as an evident cytogenetic damage in both bone marrow and peripheral blood. Interestingly, as compared to exposure to smoke only, alternate daily cycles of exposure to both light and smoke significantly increased malondialdehyde concentrations and DNA adduct levels in lung and the frequency of micronuclei in pulmonary alveolar macrophages. The oral administration of sulindac, a nonsteroidal antiinflammatory drug, attenuated several biomarker alterations due to the combined exposure of mice to light and smoke. In conclusion, the light induces a systemic genotoxic damage, which is presumably due to the UV-mediated formation in the skin of long-lived derivatives, such as aldehydes. This damage may mechanistically be involved in light-related hematopoietic malignancies. In addition, the light displayed an insofar unsuspected synergism with smoke in the induction of DNA damage in the respiratory tract.
Systemic genotoxic effects produced by light, and synergism with cigarette smoke in the respiratory tract of hairless mice
2 Department of Health Sciences, University of Genoa, via A. Pastore 1, I-16132 Genoa, Italy
3 National Cancer Institute, Rockville, Maryland 20892
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