US EPA

2210729 

Technical Report 

Mutagenic Activity of Nitrosamines in Mammalian Cells. Study with the CHO and Human Leukocyte SCE Assays 

Ho, T; San Sebastian, , JR; Hsie, AW 

1984 

NIOSH/00165399 

1 

129-147 

Ability of nitrosamines to induce sister chromatid exchanges (SCE) in a human leukocyte culture system and gene mutation in Chinese-hamster ovary (CHO) cells was studied. In the CHO hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) assay, CHO-K1-BH4 cells were used. Gene mutation was measured by determining the frequency of mutants resistant to 6-thioguanine. Mutagenic activity of promutagens was determined by coupling the S9 metabolic activation system derived from Aroclor-1254 preinduced male Sprague-Dawley-rat livers to the CHO assay. The S9 system activated promutagen nitrosodimethylamine (62759) (NDMA). Increase in NDMA mutagenicity was concentration and time dependent. Of eight nitrosamines tested, six were carcinogenic and mutagenic: nitrosomethylamine, nitrosoethylamine, nitrosomorpholine (59892), nitrosopyrrolidine (35884458), dinitroso-homopiperazine (55557001), and 4-methyl-nitroso-piperazine (15104037). The CHO/HGPRT assay showed a 100 fold difference in the mutagenic potency of five nitrosamines. Of 15 cyclic nitrosamines, 12 showed an increased frequency of SCE in the presence of S9. Nitrosopiperidines and derivatives exhibited no SCE exchange without metabolic activation. Nitrosopiperazines (NP) behaved similarly. All six carcinogenic nitrosopiperidines, except nitroso-4-piperidone (55556917), were effective SCE inducers.