Age-related negative associations between parameters of cytogenetic damage and ex vivo (+/-)-anti-benzo(a)pyrene diolepoxide-induced unscheduled DNA synthesis in smoking humans.
Chemical or physical modification of DNA may cause an increase in genomic mutations or other genetic alterations, which may ultimately result in the onset of cancer. To avoid these deleterious effects of DNA damage, humans possess DNA repair mechanisms. Decreased DNA repair, induced ex vivo by UV light or ionizing radiation in human peripheral blood lymphocytes (PBLs), has been associated with aging. The aim of this study was to investigate whether repair of DNA damage, after ex vivo exposure of PBLs obtained from smokers (n = 20) to (+/-)-anti-benzo(a)pyrene diolepoxide [(+/-)-anti-BPDE], which is a mixture of reactive metabolites from the environmental carcinogen benzo(a)pyrene, is also associated with age. Furthermore, age-related associations between ex vivo (+/-)-anti-BPDE-induced DNA repair and the frequency of endogenous cytogenetic damage (sister chromatid exchange frequencies and micronuclei frequencies) in PBLs were evaluated. A statistically significant negative association was observed between ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and age of the donors. Also, parameters of endogenous lymphocytic cytogenetic damage were negatively associated with ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and positively associated with age in this population. It is concluded that, with increasing age, a decrease in lymphocytic excision repair capacity may be responsible for increased lymphocytic DNA damage in smokers.
Stierum
R H
RH
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands. stierumr@grc.nia.nih.gov
Hageman
G J
GJ
van Herwijnen
M H
MH
van der Veer
M S
MS
Kleinjans
J C
JC
D000328:Adult; D000375:Aging / Q000235:genetics*; D001580:Benzopyrenes / Q000009:adverse effects / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000009:adverse effects / Q000494:pharmacology*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D012854:Sister Chromatid Exchange / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D001580:Benzopyrenes; D002274:Carcinogens, Environmental; D014028:Tobacco Smoke Pollution; C072019:benzo(a)pyrene diolepoxide I