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Inhibition of beta-propiolactone-induced mutagenesis and neoplasia by sodium thiosulfate
Abstract:
Studies have been initiated to find compounds that can trap direct-acting carcinogens within the stomach. Sodium thiosulfate (STS) is a potent nucleophile and in initial experiments was found to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA100 to the direct-acting carcinogens beta-propiolactone and styrene oxide. In in vitro experiments STS was shown to maintain its nucleophilicity in the acid pH range. It reacted with beta-propiolactone as rapidly at pH 2 as at pH 7.4. Thus STS has the prerequisite attributes to inhibit the carcinogenic effects of electrophiles in the stomach. Experiments were performed in which STS was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of beta-propiolactone. Under these conditions, inhibition of formation of the forestomach tumors occurred. The data obtained suggest that use of nucleophiles to protect against direct-acting carcinogens is a potential strategy for chemoprevention.
Insights
Sodium thiosulfate (STS) effectively inhibits mutagenesis from stomach carcinogens. This nucleophile shows potential for chemoprevention by trapping harmful electrophiles in the stomach.
Area of Science:
- Toxicology
- Chemoprevention
- Gastrointestinal Health
Background:
- Direct-acting carcinogens pose a risk for stomach cancer.
- Identifying compounds to neutralize these carcinogens in the stomach is crucial for prevention.
Purpose of the Study:
- To investigate the potential of sodium thiosulfate (STS) as a chemopreventive agent against direct-acting carcinogens in the stomach.
Main Methods:
- In vitro assessment of STS nucleophilicity at acidic pH.
- In vivo experiments using A/J mice treated with STS prior to carcinogen exposure.
- Evaluation of forestomach tumor formation.
Main Results:
- STS maintained nucleophilicity in acidic conditions (pH 2).
- STS significantly inhibited mutagenesis induced by beta-propiolactone and styrene oxide.
- Administration of STS before beta-propiolactone reduced forestomach tumor incidence in mice.
Conclusions:
- Sodium thiosulfate (STS) demonstrates efficacy in neutralizing direct-acting carcinogens.
- STS's ability to function in acidic environments makes it a promising candidate for stomach chemoprevention.
- Nucleophile-based strategies offer a potential approach for preventing carcinogen-induced cancers.