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Interactive mutagenicity of sodium nitrite, dimethylamine, methylurea and ethylurea
Abstract:
Groups of mice were treated per os with sodium nitrite either alone or in combination with nitrosatable amino compounds and tested in the host mediated assay. When mice were treated with sodium nitrite in combination with dimethylamine a small(4-fold) but significant increase in mutant frequency (MF) was observed. Ethylurea or methylurea in combination with sodium nitrite induced 10- or 850-fold increases in MF, respectively. The response to methylurea was dose-dependent with a 6- and 30-fold increase in MF at 5.4 and 11.5 mg/kg NaNO2 and a 6-fold increase at 108 mg/kg methylurea. That this response reflected gastric nitrosation was shown by the disappearance of the response if NaNO2 administration preceded methylurea treatment by 10 min. High MF's were observed if NaNO2 was administered 10 or 20 min after methylurea.
Insights
Sodium nitrite combined with certain amino compounds significantly increases mutant frequency in mice, indicating potential genotoxicity. The timing of administration is crucial for this gastric nitrosation effect.
Area of Science:
- Toxicology
- Genetics
- Carcinogenesis research
Background:
- Dietary intake of nitrites and amines is common.
- Nitrosatable compounds can form genotoxic N-nitroso compounds in vivo.
- The host-mediated assay is a standard method for assessing in vivo genotoxicity.
Purpose of the Study:
- To investigate the genotoxic potential of sodium nitrite in combination with nitrosatable amino compounds.
- To evaluate the effect of administration timing on genotoxicity.
- To assess the role of gastric nitrosation in the observed effects.
Main Methods:
- Groups of mice were orally administered sodium nitrite alone or with dimethylamine, ethylurea, or methylurea.
- The host-mediated assay was used to determine mutant frequency (MF).
- Dose-dependency and timing of administration were investigated.
Main Results:
- Sodium nitrite with dimethylamine caused a 4-fold increase in MF.
- Ethylurea and methylurea combined with sodium nitrite induced 10- and 850-fold increases in MF, respectively.
- The response to methylurea was dose-dependent and sensitive to the timing of sodium nitrite administration, suggesting gastric nitrosation.
Conclusions:
- In vivo formation of genotoxic N-nitroso compounds is possible when sodium nitrite is administered with specific amino compounds.
- Gastric nitrosation plays a significant role in the observed genotoxicity.
- The findings highlight the potential risks associated with co-exposure to nitrites and nitrosatable compounds.