Radiation-induced mutagenesis may derive from mechanisms common to radiation-induced cell lethality. This proposal seeks to examine this connection by correlating organic sensitizer/antitumor drug-induced radiation sensitization of cell death in populations of Salmonella typhimurium with the forward mutation frequency to 8-azaguanine resistance (modification of the Ames test) obtained from the same radio-sensitized population. A consistent correlation between these two end-points would provide evidence for common mechanisms of radiation-induced damage for the expression of both phenomena. These mechanisms may be interpreted from existing models of radiation sensitizer action. Anti-tumor drug effects in this system could then be rationally compared to organic sensitizer effects. Modelling of specific effects of organic sensitizers and anti-tumor drugs on irradiated DNA will also be done in order to aid in the mechanistic interpretation of the in vivo results. It is proposed to characterize combined radiation and organic sensitizer/anti-tumor drug effects on supercoiled SV40 DNA in aqueous solution. Resulting DNA damage will be assayed for both single-strand breaks and thymine residue release. Radiation-induced DNA base release is hypothesized by this investigator to promote mutagenesis.