Exposure of mice to cigarette smoke and/or light causes DNA alterations in heart and aorta.
Cigarette smoke (CS) is a major risk factor for cardiovascular diseases, cancer, and other chronic degenerative diseases. UV-containing light is the most ubiquitous DNA-damaging agent existing in nature, but its possible role in cardiovascular diseases had never been suspected before, although it is known that mortality for cardiovascular diseases is increased during periods with high temperature and solar irradiation. We evaluated whether exposure of Swiss CD-1 mice to environmental CS (ECS) and UV-C-covered halogen quartz lamps, either individually or in combination, can cause DNA damage in heart and aorta cells. Nucleotide alterations were evaluated by (32)P postlabeling methods and by HPLC-electrochemical detection. The whole-body exposure of mice to ECS considerably increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and of bulky DNA adducts in both heart and aorta. Surprisingly, even exposure to a light that simulated solar irradiation induced oxidatively generated damage in both tissues. The genotoxic effects of UV light in internal organs is tentatively amenable to formation of unidentified long-lived mutagenic products in the skin of irradiated mice. Nucleotide alterations were even more pronounced when the mice were exposed to smoke and/or light during the first 5 weeks of life rather than during adulthood for an equivalent period of time. Although the pathogenetic meaning is uncertain, DNA damage in heart and aorta may tentatively be related to cardiomyopathies and to the atherogenesis process, respectively.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Genoa, Italy.
D'Agostini
Francesco
F
Balansky
Roumen
R
Degan
Paolo
P
Pennisi
Tanya M
TM
Steele
Vernon E
VE
De Flora
Silvio
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000528:radiation effects; D018736:DNA Adducts / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006321:Heart / Q000528:radiation effects; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D011247:Pregnancy; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018736:DNA Adducts; D014028:Tobacco Smoke Pollution; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D020558:GTP Phosphohydrolases; D003849:Deoxyguanosine