Oxidatively damaged DNA in animals exposed to particles.
Exposure to combustion-derived particles, quartz and asbestos is associated with increased levels of oxidized and mutagenic DNA lesions. The aim of this survey was to critically assess the measurements of oxidatively damaged DNA as marker of particle-induced genotoxicity in animal tissues. Publications based on non-optimal assays of 8-oxo-7,8-dihydroguanine by antibodies and/or unrealistically high levels of 8-oxo-7,8-dihydroguanine (suggesting experimental problems due to spurious oxidation of DNA) reported more induction of DNA damage after exposure to particles than did the publications based on optimal methods. The majority of studies have used single intracavitary administration or inhalation with dose rates exceeding the pulmonary overload threshold, resulting in cytotoxicity and inflammation. It is unclear whether this is relevant for the much lower human exposure levels. Still, there was linear dose-response relationship for 8-oxo-7,8-dihydroguanine in lung tissue without obvious signs of a threshold. The dose-response function was also dependent on chemical composition and other characteristics of the administered particles, whereas dependence on species and strain could not be equivocally determined. Roles of cytotoxicity or inflammation for oxidatively induced DNA damage could not be documented or refuted. Studies on exposure to particles in the gastrointestinal tract showed consistently increased levels of 8-oxo-7,8-dihydroguanine in the liver. Collectively, there is evidence from animal experimental models that both pulmonary and gastrointestinal tract exposure to particles are associated with elevated levels of oxidatively damaged DNA in the lung and internal organs. However, there is a paucity of studies on pulmonary exposure to low doses of particles that are relevant for hazard/risk assessment.
Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. pemo@sund.ku.dk
Peter
P
Møller
Pernille Høgh
PH
Danielsen
Kim
K
Jantzen
Martin
M
Roursgaard
Steffen
S
Loft
D000818:Animals; D001194:Asbestos / Q000032:analysis / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011791:Quartz / Q000032:analysis / Q000633:toxicity
D009153:Mutagens; D037742:Nanotubes, Carbon; D052638:Particulate Matter; D001194:Asbestos; D011791:Quartz; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA