A comparative study of the bioactivation of nitrosamines to mutagens by various animal species including man

Abstract

Dimethylnitrosamine, dipropylnitrosamine, methylethylnitrosamine, nitrosopiperidine and nitrosopyrrolidine were assayed for mutagenicity in the Ames test in the presence of hepatic postmitochondrial preparations isolated from the mouse, rat, hamster, pig and man. Prior to each mutagenicity assay all activation systems were fully characterised with respect to monoamine oxidase, mixed-function amine oxidase and mixed-function oxidase activities. The hamster was the most efficient activator for all nitrosamines followed by the mouse. The latter species, however, activated nitrosopyrrolidine only weakly which was the only carcinogen readily activated by the human preparation. None of the aliphatic nitrosamines was activated by the rat or pig. No correlation was observed between efficiency of activation and any of the enzyme activities studied.

Salmonella typhimurium TA100 and TA1535 and E. coli WP2 uvrA are highly sensitive to detect the mutagenicity of short Alkyl-N-Nitrosamines in the Bacterial Reverse Mutation Test

“…Rodent CYP2E1 is known to metabolize many substrates, such as organic solvents, nitrosamines and drugs [ 20 ]. The variable levels of CYP2E1 availability and thus potency comparing rat, hamster and man resulted in different experimental results in both in vivo and in vitro studies suggesting induced hamster S9 being slightly more potent than induced rat S9 to activate nitrosamines including small N-nitrosodialkylamines [ 17 , 21 , 22 ].…”

“…In literature, there exist several reports indicating that the activation of N-Nitrosamines by the liver microsomal fraction is species dependent [ 21 , 26 , 27 ]. In general, hamster S9 was shown to highly activate some N-Nitrosamines while rat S9 sometimes failed and, in particular, it was shown that N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were mutagenic in TA1535 with hamster S9 but not with rat S9 [ 28 , 29 ].…”

Failure of the standard battery of short-term tests in detecting some rodent and human genotoxic carcinogens

“…Phillipson and Ioannides (1984) put in evidence that some nitrosamines are activated to a different extent by liver S9 obtained from different mammals; the hamster was the most efficient activator followed by the mouse. Species differences were observed in the genotoxic effects of phenacetin and paracetamol in primary cultures of hepatocytes (Holme and Søderlund, 1986).…”

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“…Distlerath and Guengerich, 1987 Buening et al, 1978;Bartsch et al, 1979;Dybing et al, 1979;Sabadie et al, 1980;Beaune et al, 1985;Mori et al, 1986;Neis et al, 1986;Raineri et al, 1986;Yamazaki et al, 1986;Jongeneelen et al, 1988;Smith andChipman, 1988 S9 S9 Ames et al, 1973;Tang and Friedman, 1977;Phillipson and Ioannides, 1983, 1984, 1989Le et al, 1985 S9 S9 S9 hazard identification Lijinsky and Andrews, 1983;Maron and Ames, 1983;Callander et al, 1995;Mortelmans andZeiger, 2000 Johnson 1996 Maron and Ames, 1983;Hakura et al, 1999Hakura et al, , 2003 S9 mix S9 10 0.5 mL S9 mix 0.05 mL S9 fraction, 1 mg protein/plate Cofactor I Ames 3 benzo a pyrene BP TA100 2-amino-3-methylimidazo 4,5-f quinoline IQ TA98 dimethylnitosamine DMN YG7108 Yamada et al, 1997 In Vitro Technologies S9 for 20 minutes with the same amount of S9 protein 1 mg/plate . The mutagenicity of BP, IQ, and DMN was assayed in the TA100, TA98, or YG7108 strain.…”