Measurement of Unscheduled DNA Synthesis In Vitro Using Primary Rat Hepatocyte Cultures

The in vitro unscheduled DNA synthesis (UDS) assay performed in primary cultures of rat hepatocytes is a useful screen for DNA damage and repair. Although it gives no direct information about the number or type of DNA lesions or about the consequences of repair, it does detect repair of the type of DNA lesions (adducts) caused by chemical carcino- gens, many of which are thought to act by interaction with macromol- ecules within the cell, particularly DNA (1) . This interaction results from the metabolism of the compound in vivo by, for example, liver mono- oxygenases, which produces a reactive electrophilic species. Such mol- ecules may interact with nucleophilic sites within the cell (2) . Since animals and humans are being exposed continuously to low levels of DNA-damaging agents, the cell has developed DNA repair systems in order to maintain the integrity of the genome. Cancer is thought to be a somatic mutational event arising either directly or indirectly from DNA damage. Agents that damage DNA, therefore, have the potential of being carcinogenic.