Flow cytometric method for scoring rat liver micronuclei with simultaneous assessments of hepatocyte proliferation

S.L. Avlasevich, S. Khanal, P. Singh, D.K. Torous, J.C. Bemis, S.D. Dertinger

Litron Laboratories

Environmental and Molecular Mutagenesis
Volume 59, Issue 3, April 2018, Pages 176-187

This publication has received the Editor’s Choice award by Environmental and Molecular Mutagenesis (EMM). 
Historically, the erythrocyte-based micronucleus test has been a cornerstone of regulatory safety testing. More recently however, there has been growing interest in the development of a liver micronucleus assay. Since the liver breaks down drugs into their metabolites this tissue is exceptionally qualified to measure exposure to these compounds.
Based on work by Litron scientists, the article describes a new method for measuring micronucleated hepatocytes via flow cytometry. For this work, Litron scientists studied diethylnitrosamine (DEN) and quinoline (QUIN) in rats. With two different study designs, results showed the compounds did not induce micronuclei in hematopoietic cells but did induce micronuclei in hepatocytes. 
Microscopic and flow cytometric results were comparable, although flow cytometry provided data in a fraction of the time. In addition to a higher throughput, flow cytometry also provided information on hepatocyte proliferation. This simultaneous measurement provides information on liver cell division, an important aspect of any micronucleus assay.