MUTAGENICITY OF HETEROCYCLIC NITROGEN MUSTARDS (ICR COMPOUNDS) IN CULTURED MAMMALIAN-CELLS

Abstract

The mutagenicity of 6 carcinogenic heterocyclic nitrogen mustards (ICR compounds) was determined in a cultured mammalian cell system using resistance to 6-thioguanine to select for mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells. The 6 compounds tested included ICR 191 [2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine dihydrochloride], 170 [2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]acridine dihydrochloride], 292 [9-[3-(ethyl-2-chloroethyl)aminopropylamino]benz[a]acridine], 372 [10-[2-chloroethylamino)propylamino]-2-methoxy-7-chlorobenzo[b][1,5]-naphthyridine], 191-OH and 170-OH. The first 4 contain a single 2-chloroethyl group (nitrogen half-mustard) on the side chain and are mutagenic, with the tertiary amine types (170 and 292) 3-5 times more mutagenic than the secondary amine types (191 and 372). The remaining compounds (191-OH and 170-OH) are not mutagenic, indicating that the 2-chloroethyl group is needed for mutation induction.