DIFFERENTIAL SUSCEPTIBILITY TO OXIDANT EXPOSURE IN INBRED STRAINS OF MICE: NITROGEN DIOXIDE VERSUS OZONE

• Published in: Inhalation toxicology Vol. 9; no. 7; pp. 601 - 621
• Main Authors: Kleeberger, Steven R, Zhang, Liu-Yi, Jakab, George J
• Format: Journal Article
• Language: English
• Published: Informa UK Ltd 1997; Taylor & Francis
• ISSN: 0895-8378; 1091-7691
• DOI: 10.1080/089583797198006

The contribution of genetic background to the pathogenesis of airway responses to environmental agents including air pollutants is becoming increasingly clear. Characterization of genetic mechanisms of response to these agents may assist in the identification of susceptible individuals and populations. The primary objective of this investigation was to utilize inbred strains of mice to determine (1) whether there was significant genetic contribution in susceptibility to lung injury and inflammation induced by single and repeated acute exposures to nitrogen dioxide (NO2) and (2) whether similar genetic factors control sus- ceptibility to lung injury induced by NO2 and another oxidant, ozone (O3). Nine strains of inbred mice (male, 5-6 wk) were studied: 129/ J, A/ J, AKR/ J, BALB/ cJ, C3H/ HeJ, C57BL/6J, DBA/2J, SJL/J, and SWR/J. Each was exposed for 3 h to filtered air (controls) or 15 ppm NO2, and cellular inflammation, epithelial injury, and cytotoxicity were measured 2, 6, and 24 h thereafter. NO2 exposure caused significant increases in cytotoxicity and lavageable macrophages, epithelial cells, polymorphonuclear leukocytes, and protein in all strains. Interstrain variation in each of these effects indicated that genetic background contributed a significant portion of the variance in responses to this oxidant. Two strains that were differentially susceptible to 3-h exposure to 15 ppm NO2\[C57BL/6J (B6), C3H/HeJ (C3)] were also exposed for 6 h/ day to 10 ppm NO2 on 5 consecutive days. Each of the responses to NO2 was completely adapted after 5 days in resistant C3 mice. Only the lavageable total protein response was adapted in susceptible B6 mice. To determine whether mechanisms of susceptibility to NO2 and O3 were the same, each strain was exposed for 3 h to filtered air or 2 ppm O3 and inflammation was assessed 6 and 24 h thereafter. Strain distribution patterns (SDPs) for responses to each oxidant were not significantly concordant and indicated that susceptibility mechanisms were different. Results of these studies suggest that there is a strong genetic component to NO2 susceptibility that is partially adaptable and significantly different from O3 susceptibility.