Comparison of mouse strains and exposure conditions in acute cigarette smoke inhalation studies

• Published in: Inhalation toxicology 2011-08, Vol.23 (10), p.602-615
• Main Authors: Tsuji, Hiroyuki, Fujimoto, Hitoshi, Matsuura, Daiki, Nishino, Tomoki, Lee, K Monica, Renne, Roger, Yoshimura, Hiroyuki
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - blood; Biomarkers - urine; bronchoalveolar lavage fluid; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Cigarette smoke; Cytokines - analysis; dosimetry; exposure regimen; Female; histopathology; Inhalation Exposure - adverse effects; Inhalation Exposure - analysis; lung inflammation; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; mouse strain; Nicotine - metabolism; Nicotine - urine; Pneumonia - etiology; Pneumonia - immunology; Pneumonia - pathology; Respiratory Rate - drug effects; Respiratory System - drug effects; Respiratory System - immunology; Respiratory System - pathology; Species Specificity; Tidal Volume - drug effects; Time Factors; Tobacco Smoke Pollution - adverse effects; Tobacco Smoke Pollution - analysis
• ISSN: 0895-8378; 1091-7691
• DOI: 10.3109/08958378.2011.596851

Cigarette smoke exposures in mice have been conducted under various exposure conditions using different strains as animal models of smoke-related diseases. We exposed cigarette smoke to two strains of mice [C57BL/6J (C57) and AKR/J (AKR)] under two different exposure regimens (1 h or 4 h/day) at equivalent daily exposure amount (concentration × time). After 2 weeks exposure, mice were evaluated using exposure markers and biological responses. Smoke exposure suppressed respiratory parameters dependent on exposure concentration. The 1-h regimen groups generally showed a greater degree of respiratory suppression and relatively lower exposure markers of urinary nicotine metabolites than the corresponding 4-h regimen groups. Tidal volume was more suppressed in AKR compared to C57, while respiratory rate was more suppressed in C57. Plasma exposure markers and respiratory parameters suggested that C57 inhaled more volume of smoke than AKR. Changes in bronchoalveolar lavage fluid (BALF) cytology and enzyme parameters were most noticeable in the 1 h AKR groups. In BALF cytokine concentration, TARC concentration in C57 was higher than AKR, while KC and MCP-1 in AKR were higher than C57. Relative lung/body weight ratio in smoke-exposed C57 was generally higher, as well as the incidence and severity of lesions in respiratory organs compared to AKR. In summary, C57 appeared to inhale relatively more smoke and displayed greater inflammatory changes in respiratory tract than AKR. Comparison of exposure regimens suggests that a longer exposure duration at lower WTPM concentration might deliver a larger dose of smoke than a shorter exposure duration at higher WTPM concentration.