Integration of liver and blood micronucleus and Pig-a gene mutation endpoints into rat 28-day repeat-treatment studies: Proof-of-principle with diethylnitrosamine.

ABSTRACT: Regulatory guidance documents stress the value of assessing multiple tissues and the most appropriate endpoints when evaluating chemicals for in vivo genotoxic potential. However, conducting several independent studies to consider multiple endpoints and/or tissue compartments is resource intensive. Furthermore, conventional approaches for scoring genotoxicity endpoints are slow, tedious, and less objective than what would be considered ideal. In an effort to address these issues with current practices, we attempted to i) employ flow cytometry-based methods to score liver micronuclei, blood micronuclei, and blood Pig-a gene mutation, and ii) integrate the endpoints into a common general toxicology study design-the rat 28-day repeat dose study. A proof-of-principle experiment was performed w

SUBMITTER: Khanal S 

PROVIDER: S-EPMC5896020 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature