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Published on: February 5, 2015
Antimutagenic effect of isocyanates and related compounds in Escherichia coli
Abstract:
Isocyanates and isothiocyanates have been suggested to inactivate enzymes involved in the metabolic activation of chemical carcinogens and the repair of DNA damage. These compounds decrease the mutability of a tester strain of Escherichia coli B under UV irradiation. This paper deals with the antimutagenicity of acylating agents, including isocyanates and isothiocyanates, and some anti-oxidants which are suspected to be anticarcinogenic. The results can be summarized as follows. (1) The antimutagenic effect observed in the present study operates on UV-induced mutagenesis but not on X-ray-induced mutagenesis. (2) This effect operates only on the wild-type strain, H/r30R, but not on Hs30R deficient in the excision repair system. (3) This effect may function through giving the irradiated cells a greater chance to carry out excision repair by prolonging the lag-period before entry into the S-phase. (4) The carbamoylating ability of isocyanates and isothiocyanates may be responsible for the antimutagenicity, but other type of reactivities may also be involved. These antimutagens also participate in inactivating enzymes relevant to the metabolic activation of mutagens, resulting in a decrease in the frequency of chemically induced mutagenesis.
Insights
Acylating agents like isocyanates and isothiocyanates show antimutagenic properties against UV-induced mutations in wild-type bacteria. This effect is linked to DNA repair mechanisms and enzyme inactivation, not X-ray mutagenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Isocyanates and isothiocyanates are known to inactivate enzymes involved in carcinogen metabolism and DNA repair.
- These compounds have demonstrated a reduction in the mutability of Escherichia coli B under UV irradiation.
Purpose of the Study:
- To investigate the antimutagenic effects of acylating agents, including isocyanates and isothiocyanates, and antioxidants.
- To elucidate the mechanisms underlying the observed antimutagenicity, particularly concerning DNA repair and mutagenesis.
Main Methods:
- Testing the antimutagenic effects of acylating agents on UV- and X-ray-induced mutagenesis.
- Comparing the effects on wild-type bacterial strains versus those deficient in DNA excision repair.
Main Results:
- The antimutagenic effect was observed for UV-induced mutagenesis but not for X-ray-induced mutagenesis.
- The effect was significant in the wild-type strain (H/r30R) but absent in the excision repair-deficient strain (Hs30R).
- The carbamoylating ability of these agents is a potential mechanism, possibly by enhancing DNA repair or inactivating mutagenic enzymes.
Conclusions:
- The antimutagenicity of isocyanates and isothiocyanates is dependent on functional DNA excision repair pathways.
- These compounds may act by prolonging the lag phase before DNA replication, allowing more time for repair.
- Inactivation of enzymes involved in mutagenic activation contributes to their antimutagenic and potentially anticarcinogenic properties.
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