Recent progress in liver micronucleus test

TONG Wen; ZHOU Chang-hui; CHANG Yan

Abstract：Liver micronucleus (MN) assays are highly sensitive in predicting hepatocarcinogenicity and useful in evaluating genotoxic substances that target the liver.In comparison with bone marrow MN assay,liver MN assay can detect unstable mutagens or promutagens with short-lived metabolites.Liver MN assay includes three major methodologies as following.① Partial hepatectomy (PH) method which is the first been developed.Because the methodology requires intensive labor and a possible interaction between the mitogen and the substance,it has not been used as a routine method to evaluate chemical genicity in the liver.② Juvenile/young rat (JR) method,the liver in juvenile rat has higher cell proliferation than in adult rat liver,so livers in young rats would have sufficient numbers of replicating cells to provide sensitivity for detecting MN.③ Repeated-dose (RD) method which has already been tested by international collaborative study using accumulative effect of multiple dosing.It can compensate for the lower mitotic activity and can be integrated into a general toxicological study,thereby reducing the numbers of animals required.Here the development of liver micronucleus assays were introduced,and the strength and weakness of the three methodologies were also demonstrated.These may provide some key references for the application of liver micronucleus assay.