Age and Gender Effects on Genotoxicity in Diesel Exhaust Particles Exposed C57BL/6 Mice

年龄和性别对柴油机尾气颗粒暴露的 C57BL/6 小鼠遗传毒性的影响

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作者:Joong Won Lee, Jin Sik Kim, Hee Jae Lee, Ji-Hye Jang, Ja-Hyun Kim, Woo Jong Sim, Yong-Beom Lim, Ji-Won Jung, Hyun Joung Lim

Abstract

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM2.5) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM2.5 induced genomic damage. Here, we assessed the DNA damage potency of PM2.5 using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks. Mice were intratracheally instilled with diesel exhaust PM2.5 (DEP, NIST SRM 1650b), twice a week for 4 weeks. Exposure to DEP was not associated with an increase in the frequency of micronucleated polychromatic erythrocytes and did not induce a systemic genotoxic effect in the bone marrow. Meanwhile, the results from the comet assay showed a significant increase in DNA damage in DEP exposed mouse lung specimens. The positive relationship between DEP exposure and DNA damage is stronger in the older than in the younger group. Statistical analysis showed that there was a modifying effect of age on the association between PM2.5 exposure and DNA damage. Our results suggest that the age factor should be considered to better understand the cellular adverse effects of PM2.5.

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