, Volume 86, Issue 3, pp 509-516

Dose-related cytogenetic damage in pulmonary alveolar macrophages from mice exposed to cigarette smoke early in life

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Abstract

The micronucleus test detects both structural and numerical chromosomal aberrations caused by environmental agents. However, this test is poorly sensitive to detect the clastogenicity of cigarette smoke (CS) in human peripheral blood lymphocytes. At variance with peripheral blood lymphocytes and other cells outside the lower respiratory tract, pulmonary alveolar macrophages (PAM) are selectively affected by inhalable carcinogens and have been used to evaluate the modulation of CS-related cytogenetic alterations in vivo. The present study was aimed at evaluating (1) the cytogenetic response in PAM isolated from the lung of mice exposed to CS during the first 4 weeks of life and (2) the dose dependence of MN and polynucleated (PN) PAM formation in CS-exposed mice. To this purpose, ICR(CD-1) mice were exposed whole body to mainstream CS for 4 weeks, starting immediately after birth. Bronchoalveolar lavage (BAL) was performed to evaluate the cellularity of this fluid and the frequency of PN and MN PAM. At the doses of 119, 292, and 438 mg/m3 total particulate matter, CS significantly increased both the proportion of PAM in the BAL fluid and the frequencies of PN and MN PAM. The cytogenetic effects were significantly correlated with the CS dose. In conclusion, PAM are suitable to detect induction by CS of clastogenic and aneugenic effects in mice during a developmental period corresponding to infancy, childhood, and early adolescence in humans. These surrogate cells, providing an important defense mechanism of the respiratory tract, are proposed as indicators of CS-related DNA damage in youngsters.