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Folate deficiency followed by ionizing radiation perturbs hepatic dihydrofolate reducatse activity
Author(s) -
Batra Vipen,
Lakhmy Seetha,
Devasagayam Thomas Paul Asir
Publication year - 2008
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520340403
Subject(s) - dihydrofolate reductase , dna damage , biochemistry , ionizing radiation , dna , dna repair , nucleic acid , purine , enzyme , ap site , nucleic acid metabolism , chemistry , biology , rna , irradiation , physics , gene , nuclear physics
There is lot of interest in the folate metabolism because of the essential role of folate coenzymes in nucleic acid synthesis. Gamma (γ) radiation is well known for inducing damage in the DNA. To counteract these damage, a variety of DNA repair pathways have evolved that require regular supply of DNA bases whose biosynthesis in turn depends on sufficient pools of folate dependent enzymes like dihydrofolate reductase (DHFR). In the present study, we examined the ionizing radiation mediated perturbation of DHFR activity in folate deficient and folate sufficient conditions. In folate deficient animals a potent inhibition of liver DHFR activity was observed. Our results showed that combination of folate starvation and ionizing radiation might adversely affect the DHFR activity, compared to their individual treatments. Measurement of apurinic/apyrimidinic sites (AP sites), a major type of DNA damage generated by radiation induced loss of purine and/or pyrimidine base, indicated a dose dependent DNA damage in folate deficient animals. In conclusion our data suggest an interactive role of folate deficiency and radiation injury in inhibiting DHFR activity.