Chemoprotection profiles of sodium thiosulfate on methyl methanesulfonate-induced mutagenesis of bacteriophage T4.
BACKGROUND
The alkylation of nucleic acids is primarily responsible for chemical carcinogenesis. Even during disease treatment, several alkylating drugs interact with nucleic acids and cause severe toxic effects. Thus good chemoprotectants are necessary. For our study we chose a simple model organism, bacteriophage T4 (a nucleoprotenic particle), and alkylating agent methyl methanesulfonate (MMS) to study its lethal effects. Sodium thiosulfate (STS), used as a chemoprotectant, has been tested against alkylating drugs.


METHODS
Bacteriophage T4D(o) were exposed to different molarities of MMS for several pre-termination incubations. Alkylation reactions were stopped with different concentrations of STS at given pre-termination incubation periods and further incubated up to 24 hours. The viability (survival frequency) of phage T4 was studied at various post-termination intervals by plaque count assay.


RESULTS
Our results show that the survival frequency is strongly influenced by MMS dosage and exposure time. However, the antidotal effect of STS on MMS-induced lethality directly corresponds to STS dosage. Survival frequencies with 1% quench solution were lower than with 5% quench solution at all molarities of MMS and at different pre- and post-termination periods.


CONCLUSIONS
Our studies confirmed the role of STS in the cytoprotection of bacteriophage T4. In the presence of 1% STS, a moderate inhibition in cytotoxicity was observed, while 5% STS exhibited a significant inhibition against the cytotoxic activity of MMS, presumably due to a rapid covalent binding of the methyl group (carbocation - an electrophile) of MMS with the nucleophilic sulfur atom of STS.
Malik
Ajmaluddin
A
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India. sunillal@icgeb.res.in
Khan
Asad Ullah
AU
Lal
Sunil Kumar
SK
D017122:Bacteriophage T4 / Q000187:drug effects* / Q000235:genetics; D008741:Methyl Methanesulfonate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016296:Mutagenesis; D013885:Thiosulfates / Q000494:pharmacology*
D013885:Thiosulfates; D008741:Methyl Methanesulfonate; C017717:sodium thiosulfate