Abstract
N-Nitrosodimethylamine (NDMA), but not N-nitroso-N-methylurea (MNU) was more mutagenic in the Salmonella hisG428 strain, TA104, than in the hisG46 strain, TA100 in the presence of rat or hamster liver S-9 mix. As both NDMA and MNU can give rise to methyldiazonium ion (MDI) it appears that NDMA can be metabolized to an additional mutagen with a higher activity in TA104. The effects of W and error-prone repair on NDMA and MNU-induced mutagenesis in TA104 were also different. α-Acetoxy-NDMA, which gives rise to the NDMA metabolite, α-hydroxy-NDMA, was more mutagenic in TA104 than TA100, under certain conditions. Several metabolites of NDMA (formaldehyde, 1,1-dimethylhydrazine and nitrite) were not significantly mutagenic at the concentrations that could have been generated from NDMA. It was previously reported that the microsomal-mediated mutagenesis induced by NDMA is greatly increased by cytosol in TA104, but not in TA100. The current study found that when cytosol was separated into a high and a low mol. wt fraction, neither greatly enhanced microsomal-mediated mutagenesis by NDMA in TA104. Addition of NAD to the high, but not the low mol. vt fraction resulted in greatly enhanced activation of NDMA to a mutagen in TA104. The enhancement by cytosol of NDMA-induced mutagenesis in hisG428 was only observed when both microsomes and cytosol were simultaneously present. These observations indicate that (i) the precursor to the ultimate mutagen is relatively short-lived; and (ii) the metabolism of α-hydroxy-NDMA to a secondary mutagenic metabolite, possibly N-nitroso-N-methylformamide, by alcohol dehydrogenase may be responsible for the ultimate mutagen with relatively high activity in TA104.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1013-1019 |
| Number of pages | 7 |
| Journal | Carcinogenesis |
| Volume | 14 |
| Issue number | 5 |
| State | Published - 1993 |
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ASJC Scopus subject areas
- Cancer Research
- Physiology
- Statistics, Probability and Uncertainty
- Applied Mathematics
- Physiology (medical)
- Behavioral Neuroscience
Cite this
Effects of cytosol on mutagenesis induced by N-nitrosodimethylamine, N-nitrosomethylurea and α-acetoxy-N-nitrosodimethylamine in different strains of Salmonella : Evidence for different ultimate mutagens from N-nitrosodimethylmine. / Guttenplan, Joseph.
In: Carcinogenesis, Vol. 14, No. 5, 1993, p. 1013-1019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of cytosol on mutagenesis induced by N-nitrosodimethylamine, N-nitrosomethylurea and α-acetoxy-N-nitrosodimethylamine in different strains of Salmonella
T2 - Evidence for different ultimate mutagens from N-nitrosodimethylmine
AU - Guttenplan, Joseph
PY - 1993
Y1 - 1993
N2 - N-Nitrosodimethylamine (NDMA), but not N-nitroso-N-methylurea (MNU) was more mutagenic in the Salmonella hisG428 strain, TA104, than in the hisG46 strain, TA100 in the presence of rat or hamster liver S-9 mix. As both NDMA and MNU can give rise to methyldiazonium ion (MDI) it appears that NDMA can be metabolized to an additional mutagen with a higher activity in TA104. The effects of W and error-prone repair on NDMA and MNU-induced mutagenesis in TA104 were also different. α-Acetoxy-NDMA, which gives rise to the NDMA metabolite, α-hydroxy-NDMA, was more mutagenic in TA104 than TA100, under certain conditions. Several metabolites of NDMA (formaldehyde, 1,1-dimethylhydrazine and nitrite) were not significantly mutagenic at the concentrations that could have been generated from NDMA. It was previously reported that the microsomal-mediated mutagenesis induced by NDMA is greatly increased by cytosol in TA104, but not in TA100. The current study found that when cytosol was separated into a high and a low mol. wt fraction, neither greatly enhanced microsomal-mediated mutagenesis by NDMA in TA104. Addition of NAD to the high, but not the low mol. vt fraction resulted in greatly enhanced activation of NDMA to a mutagen in TA104. The enhancement by cytosol of NDMA-induced mutagenesis in hisG428 was only observed when both microsomes and cytosol were simultaneously present. These observations indicate that (i) the precursor to the ultimate mutagen is relatively short-lived; and (ii) the metabolism of α-hydroxy-NDMA to a secondary mutagenic metabolite, possibly N-nitroso-N-methylformamide, by alcohol dehydrogenase may be responsible for the ultimate mutagen with relatively high activity in TA104.
AB - N-Nitrosodimethylamine (NDMA), but not N-nitroso-N-methylurea (MNU) was more mutagenic in the Salmonella hisG428 strain, TA104, than in the hisG46 strain, TA100 in the presence of rat or hamster liver S-9 mix. As both NDMA and MNU can give rise to methyldiazonium ion (MDI) it appears that NDMA can be metabolized to an additional mutagen with a higher activity in TA104. The effects of W and error-prone repair on NDMA and MNU-induced mutagenesis in TA104 were also different. α-Acetoxy-NDMA, which gives rise to the NDMA metabolite, α-hydroxy-NDMA, was more mutagenic in TA104 than TA100, under certain conditions. Several metabolites of NDMA (formaldehyde, 1,1-dimethylhydrazine and nitrite) were not significantly mutagenic at the concentrations that could have been generated from NDMA. It was previously reported that the microsomal-mediated mutagenesis induced by NDMA is greatly increased by cytosol in TA104, but not in TA100. The current study found that when cytosol was separated into a high and a low mol. wt fraction, neither greatly enhanced microsomal-mediated mutagenesis by NDMA in TA104. Addition of NAD to the high, but not the low mol. vt fraction resulted in greatly enhanced activation of NDMA to a mutagen in TA104. The enhancement by cytosol of NDMA-induced mutagenesis in hisG428 was only observed when both microsomes and cytosol were simultaneously present. These observations indicate that (i) the precursor to the ultimate mutagen is relatively short-lived; and (ii) the metabolism of α-hydroxy-NDMA to a secondary mutagenic metabolite, possibly N-nitroso-N-methylformamide, by alcohol dehydrogenase may be responsible for the ultimate mutagen with relatively high activity in TA104.
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M3 - Article
VL - 14
SP - 1013
EP - 1019
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 5
ER -