Analysis of N-nitrosamines for genotoxicity in primary hepatocytes derived from various species.
DNA single-strand breaks (SSB) were induced in metabolically competent primary hepatocytes from rats, hamsters and pigs by a series of N-nitrosamines with organ-specific activities. Both hepatotrophic and nonhepatotropic carcinogens were genotoxic in the liver cells of all three species. Nonhepatotropic compounds were active at relatively lower doses than liver carcinogens in all species tested, substantiating many previous findings that organ-specific activation is not the primary determining factor of organ susceptibility to cancer. In 11 experiments of almost identical quality, the degree of SSB induced by 6.25 mumol N-nitrosodimethylamine varied by 75%. This high interindividual variability, even among hepatocytes derived from a single rat strain, indicates that the slight differences seen between rat, hamster and pig hepatocytes are not necessarily due to differences in species susceptibility.
Schmezer
P
P
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Pool
B L
BL
Preussmann
R
R
Schmähl
D
D
D000818:Animals; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity; D013552:Swine
D004277:DNA, Single-Stranded; D009602:Nitrosamines