Inhaled benzene increases the frequency and length of lacI deletion mutations in lung tissues of mice.

This study investigated the frequency and pattern of mutations that arose in lacI transgenes in lung tissues of mice exposed to 300 p.p.m. of benzene for 6 h/day x 5 days/week for 12 weeks. The nucleotide sequence changes in 86 lacI- transgenes from lung tissues of eight benzene-exposed mice (BEM) and 78 spontaneous lacI- transgenes from lung tissues of eight unexposed control mice (UCM) were identified and compared. A total of 31% (27/86) of the lacI mutations in BEM are deletions compared with 9% (7/78) deletions in UCM. In BEM, 44% (12/27) of the deletions were longer than 10 bp, whereas only 14% (1/7) of the deletions in UCM exceeded 10 bp in length. Statistical tests supported the hypothesis that benzene exposure resulted in significant increases in both the frequency and length of deletions. Based on the lacI mutant frequency and fraction of unique mutations, lung tissues of BEM were estimated to have a 1.8-fold increase in lacI mutation frequency compared with lung tissues of UCM. The results presented in this paper demonstrate that inhaled benzene is a gene mutagen in lung tissues of mice.