Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity.

ABSTRACT:

Background

Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers.

Objective

We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that influence benzene-induced genotoxicity.

Methods

We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). The study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis.

Results

SUBMITTER: French JE 

PROVIDER: S-EPMC4348743 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature