Vitro Test for Unscheduled DNA Synthesis in Rat Hepatocytes

Until recently, most regulatory guidelines have focused mainly on tests for gene mutations and structural chromosome damage. HowevCT, the validation of the in vitro micronucleus test and the development of an OECD gnideline indicates that its use will become much more widespread (OECD 2007). 

It will continue to be of considerable importance to establish a specific role for chromosome loss in tumor development. The analysis of aneuploidy in interphase cells of solid tumors using FISH will be greatly advantageous in this respect. For cancer risk assessment purposes, results from aneuploidy assays can be considered particularly useful when the mode of action of a chemical is known to result in chromosome loss or nondisjunction. 

Because the liver is the major organ of xenobiotic metabolism, hepatocytes are an appropriate cell in which to conduct genotoxicity tests. Because they do not divide readily in culture, they are not so useful in tests for chromosomal aberrations or mutations, but they can be used to detect DNA damage or repair where dividing cells are not needed. In studies with fresh hepatocytes, it is not necessary to include S9 mix. 

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