Folate deficiency followed by ionizing radiation perturbs hepatic
dihydrofolate reducatse activity
Issue title: Integrated Functions of Diet in Anti-Aging and
Cancer Prevention: Papers from the 4th International Niigata Symposium on Diet
and Health, 20–30 November 2008, Niigata, Japan
Affiliations: Radiation Biology and Health Sciences Division, Bhabha
Atomic Research Centre, Mumbai, India
Note: [] Address for correspondence: Vipen Batra, Radiation Biology and
Health Sciences Division, Modular Laboratories, Room No. 3-47-S, Bhabha Atomic
Research Centre, Mumbai – 400 085, India. Tel.: +91 22 25590411; Fax: +91
22 25560750/+91 22 25505151; E-mail: [email protected]
Abstract: 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.
Keywords: γ-radiation, folate, dihydrofolate reductase, mice, starvation, AP sites
DOI: 10.3233/BIO-2009-1081
Journal: BioFactors, vol. 34, no. 4, pp. 273-283, 2008
