Effect of L-carnitine on nucleic acid status of aged rat brain.

The accumulation of damage to DNA plays a significant role in the etiology of the aging process. The importance of nutrition in delaying the aging process is well recognized. L-carnitine is a quaternary ammonium compound heterogeneously distributed in the brain. In the present study the effect of L-carnitine on DNA damage of various brain regions was investigated in a duration dependent way. Male albino rats aged 4 and 24 months were administered L-carnitine (300 mg/kg body weight/day) for 7,14 and 21 days. The activities of antioxidant enzymes, the levels of nucleic acids and the extent of DNA damage were measured in cortex, hippocampus, striatum, hypothalamus and cerebellum. Our results clearly showed that the activities of super oxide dismutase, glutathione peroxidase and the levels of DNA and RNA were significantly low in cortex, hippocampus and striatum of aged rat brain when compared with that of young rats. The regions that have lower antioxidants status are highly susceptible to oxidative DNA damage. Treatment with L-carnitine in aged rats enhanced the nucleic acid, antioxidant activity in a duration dependent manner with maximal effect after 21 days whereas no significant changes could be observed in the brain of young rats. These results suggest that that L-carnitine administration prevents age-related increment of DNA damage, thereby confirming the neuroprotective action of L-carnitine against aging.

Comparison of inter- and intra-chromosomal aberrations in blood samples exposed to different dose rates of gamma radiation.

Peripheral blood samples obtained from a normal healthy volunteer were exposed in vitro to gamma radiation with various doses at different dose rates of 1.0, 0.1 and 0.0014 Gy min(-1). The exposed samples were analysed for different chromosomal aberrations such as dicentrics (DC), centric rings (CR) and double-minutes (DM). The ratio of DC chromosomes (inter) to the total number of centric rings (CR) and double-minutes (DM) (CR + DM = intra) were analysed for all the three dose rates. The study showed that the frequency of inter-arm chromosomal aberrations was more then three times higher than that observed with intra-arm chromosomal aberrations in samples exposed at a dose rate of 1.0 and 0.1 Gy min (-1). However, the frequency of inter- and intra-arm chromosomal aberrations were almost same (ratio 1:1) in samples exposed at a dose rate of 0.0014 Gy min(-1). This paper discusses the usefulness of the ratio of inter- and intra-arm chromosome aberration in finding out whether the sample was exposed to high or low dose rate radiation.

Comparison of chronic exposures received by radiation workers using different biological end-points with the doses recorded by TLD.

The frequency of different biological end-points such as translocation, dicentrics (DC) and micronuclei (MN) was studied in 14 radiation workers and 21 non-radiation workers. The average frequencies for different types of aberrations were significantly higher in radiation workers compared to those of respective aberrations in non-radiation workers. Out of 14 radiation workers, eight subjects showed a dose above the detection limit as per translocation and seven subjects as per DC frequency and no patient showed a dose above the detection limit as per MN frequency. Regression analysis carried out between the recorded doses according to Thermo Luminescence Dosimeter (TLD) and the dose estimated as per translocation frequency gave a correlation coefficient of 0.32, whereas that obtained with TLD dose and the dose estimated as per DC was 0.81. When the correlation was made between the TLD dose, which was above 0.15 Gy (the detection limit for translocation), and the dose estimated as per translocation frequency in these subjects, a correlation coefficient of 0.98 was found. A similar analysis between the TLD dose above 0.5 Gy (the detection limit for DC) and the dose estimated as per DC frequency in these subjects, a correlation coefficient of 0.26 resulted. This paper discusses the reasons for the poor correlation obtained between TLD dose and dose estimated as per DC and MN frequency.

Comparison of UV-induced unscheduled DNA synthesis in lymphocytes exposed to low doses of ionising radiation in vivo and in vitro.

In an attempt to understand and ascertain the stimulatory effects of low-dose ionising radiation, a study was conducted to compare the changes in the UV-induced repair capacity of human blood cells exposed to low conditioning doses of ionising radiation under in vivo and in vitro conditions. A significant increase in the rate of UV induced Unscheduled DNA synthesis (UDS) in lymphocytes pre-exposed to low doses of ionising radiation was observed both under in vitro and in vivo conditions. There was also a significant correlation between the adapting dose and net UDS in lymphocytes of radiation workers implying that the triggering action of the adaptation process is dose dependent. However, on comparing the extent of UV-induced UDS of the in vivo and in vitro exposures, significantly higher rates of UDS were observed in the lymphocytes of radiation workers when compared to a corresponding in vitro adapting dose. We postulate that the response in vivo is much more pronounced due to cell repopulating events and extra cellular secretory factors like hormones etc,.

Estimation of dose in cancer patients treated with fractionated radiotherapy using translocation, dicentrics and micronuclei frequency in peripheral blood lymphocytes.

The frequency of translocation, dicentrics (DC) and micronuclei (MN) was studied in blood samples exposed in vitro to (60)Co gamma radiation and cervical cancer patients undergoing fractionated radiotherapy. The samples exposed under in vitro condition showed that the frequency of translocation and dicentric followed Poisson distribution ('u' varied between -0.04 and +1.41 for translocation and between -0.09 and +1.81 for DC) and that obtained with MN follow over dispersion ('u' varied between +2.04 and +9.28). However, the cervical cancer patients undergoing radiotherapy showed over dispersion for all these three aberrations (DC, MN and translocation). The frequencies of aberrations obtained in cancer patients were found to be lower than those obtained for in vitro exposure for doses more than 2 Gy equivalent whole body dose (EWBD). The dose-response curves were constructed using the frequencies of DC, MN and translocation as a function of EWBD. Doses as measured from the dose response curves were compared with the estimated dose in order to check whether the measured and estimated doses agree. The percent variation between the doses measured from aberration frequencies and that of the estimated dose was lower with translocation (10.8+/-7.41%) compared to those obtained with DC (38. 08+/-31.85%) and MN (47.19+/-31.80%).

Higher frequency of dicentrics and micronuclei in peripheral blood lymphocytes of cancer patients.

The presence of dicentric chromosome (DC) and micronuclei (MN) frequency in the peripheral blood lymphocytes of 25 cancer patients prior to chemo and radiotherapy and 21 healthy volunteers were studied. The overall DC and MN showed significantly higher frequency compared to those obtained in normal healthy volunteers (p<0.0001). However, among 25 patients only 15 showed a higher frequency of DC aberration, nine patients showed the presence of minutes (M) and seven patients showed chromatid breaks (ChB). The reasons for the higher frequency of aberration observed in these cancer patients are discussed in this paper.

Influence of in vitro low-level gamma-radiation on the UV-induced DNA repair capacity of human lymphocytes--analysed by unscheduled DNA synthesis (UDS) and comet assay.

Unscheduled DNA synthesis (UDS) induced by ultraviolet radiation (UV) was studied in human lymphocytes after exposing blood samples in vitro to doses ranging between 1 and 10 mGy gamma-radiation, by way of measuring tritiated thymidine (3H-TdR) uptake in the DNA of these lymphocytes. The results indicate that samples pre-exposed to gamma-ray doses ranging between 2.5 and 4 mGy show higher UDS levels compared with those pre-exposed to doses of less than 2.5 or more than 4 mGy. These results were verified by studying the rate of removal of UV-induced photoproducts using the comet assay. The reason for the increase in DNA repair capacity in this dose range is discussed in comparison with earlier reports on this phenomenon. The DNA repair capacity with respect to inter-individual variability and age is also analysed. The study implies that the comet assay is a simple and sensitive visual method to track nucleotide excision repair and hence can be used to estimate UV-induced DNA repair in the place of the more reliable yet cumbersome and time-consuming, grain-counting autoradiographic technique.