Mutagenesis of intact parvovirus H-1 is expressed co-ordinately with enhanced reactivation of ultraviolet irradiated virus in human and rat cells treated with 2-nitronaphthofurans.

Abstract

The exposure of human or rat cells to non-toxic concentrations of two 2-nitronaphthofuran derivatives activated co-ordinately the transient expression of mutator and repair activities. These activities gave rise to both an increase in the mutagenesis (enhanced mutagenesis, EM) and survival (enhanced reactivation, ER) of unirradiated and u.v.-irradiated parvovirus H-1 used as respective probes. The kinetics of expression was the same for mutator and repair activities and for the two chemicals studied. The dose-responses of these activities were also parallel for a given chemical, but one of the furan derivatives exerted its inducing effect at concentrations 20-25 times lower than the other derivative. Both EM and ER were depressed by cycloheximide, and inhibitor of de novo protein synthesis. This is the first report which shows that chemicals can enhance the mutagenesis of undamaged DNA by activating the expression of mutator functions in mammalian, including human, cells. The ability of the two 2-nitronaphthofuran derivatives to trigger EM and ER was found to correlate with their reported mutagenicity in a conventional bacterial test system.