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Biomedical subjects

U Madhvanath

Publications and source records attributed to U Madhvanath.

At least 19 recordsLinked to original sources

Genotoxicity of selenite in diploid yeast.

Selenite, a chemical of industrial importance and also an antimutagenic/anticarcinogenic agent, was tested for mutagenic and recombinogenic effects in 2 diploid yeast strains, Saccharomyces cerevisiae BZ 34 and D7. Selenite induced gene conversion and toxicity in BZ 34 and a variety of genetic events, viz. back-mutation, gene conversion, mitotic crossing-over, aberrant colony formation and also toxicity in the D7 strain. In both strains, the genetic effects of selenite showed a peak and a decline during 5 h of treatment while its toxicity increased marginally during 1-5 h. In the BZ 34 strain, the presence of glutathione (GSH) during selenite treatment greatly enhanced the convertogenic and toxic effects of selenite.

Chemical Phenomena↗

Combined mutagenic action of chemicals and radiation in diploid yeast.

The interaction between the mutagenic action of chemicals and radiation was studied by using a diploid yeast strain Saccharomyces cerevisiae BZ 34 with mitotic gene conversion as the end-point. The cells were treated with EMS, MMS or 4-NQO alone or in combination with gamma-radiation. The 2 alkylating agents EMS and MMS produced an additive mutagenic response, whereas 4-NQO exhibited an antagonistic effect in the combined treatment with gamma-radiation.

4-Nitroquinoline-1-oxide↗

Use of the FBX dosemeter for the calibration of cobalt-60 and high-energy teletherapy machines.

The doses from the cobalt-60 teletherapy machines were measured using the FBX and secondary-standard dosemeters of Farmer-Baldwin type. The FBX dosemeter contained 0.20 mM ferrous ammonium sulphate, 5.0 mM benzoic acid and 0.20 mM xylenol orange in 0.05 N sulphuric acid. The values were compared with the values from a Fricke dosemeter and a graphite chamber used as primary standards. The values of the FBX, Fricke and graphite chambers agreed. There were, however wide differences among the different secondary-standard dosemeters themselves and with the FBX dosemeter. The FBX dosemeter was used for the measurement of central axis depth dose distributions for 5, 8, 10, 20 and 30 MeV electron and 42 MV x-ray beams.

Cobalt Radioisotopes↗

Comparison of sensitivity of rad mutants of diploid yeast to heat and gamma radiation: cellular target for heat inactivation.

Wild type and radiation-sensitive mutants rad 53, 54 and 55 of the diploid yeast Saccharomyces cerevisiae, in stationary and log phase were exposed to gamma radiation and hyperthermia (51 degrees C) in order to compare their sensitivity to these agents. The wild type diploid strain exposed to gamma rays showed a sigmoidal survival curve both in stationary and log phase cultures. Log phase cells were significantly more resistant than stationary phase cells. When compared to wild type, the gamma radiation response of the mutants indicated that the mutations in these RAD loci render the cells sensitive in stationary phase and very sensitive in log phase. The response of mutants to hyperthermia was similar to that of wild type cells in both the phases. The log phase cells of both wild type and mutants wee gamma radiation response of the mutants indicated that the mutations in these RAD loci render the cells sensitive in stationary phase and very sensitive in log phase. The response of mutants to hyperthermia was similar to that of wild type cells in both the phases. The log phase cells of both wild type and mutants wee gamma radiation response of the mutants indicated that the mutations in these RAD loci render the cells sensitive in stationary phase and very sensitive in log phase. The response of mutants to hyperthermia was similar to that of wild type cells in both the phases. The log phase cells of both wild type and mutants were more sensitive to heat than stationary phase cells. These results suggest that the RAD loci are not involved in the repair of hyperthermic damage. Since it is known that the products of the RAD genes are involved in the repair of DNA damage, the wild type response of these rad mutants to hyperthermia indicates that the DNA may not be the principal target for hyperthermic killing. Furthermore, the enhanced thermal sensitivity of log phase cells, containing higher amounts of active enzymes and sensitive membrane, strongly suggests that proteins and/or membranes could be the primary targets for thermal inactivation.

Cell Survival↗

Modification of high LET radiation-induced damage and its repair in yeast by hypoxia.

The lethal response of a diploid yeast strain BZ34 to densely ionizing radiations from the reaction 10B(n, alpha)7 Li was studied. The values for relative biological effectiveness (r.b.e.) and oxygen enhancement ratio (o.e.r.) for this radiation compare favourably with the data obtained with charged particles on the same strain of yeast. Recovery from potentially lethal damage was also studied by post-irradiation holding under non-nutrient conditions. In order to understand the role of oxygen in the recovery process, the investigation covered the following treatment regimens: (a) aerobic irradiation and aerobic holding (A-A), (b) aerobic irradiation and hypoxic holding (A-H), (c) hypoxic irradiation and hypoxic holding (H-H) and (d) hypoxic irradiation and aerobic holding (H-A). It has been found that the presence of oxygen is essential for recovery from the damage induced by both gamma rays and high linear energy transfer (LET) radiations. The extent of recovery was larger for gamma-induced damage than for damage induced by high LET radiation (alpha + 7Li) for the A-A condition. In the H-H condition, while only a slight recovery was seen for gamma-induced damage, it was totally absent for high LET damage. For the modality A-H, it was found that there is not recovery from the sparsely ionising gamma radiation-induced damage. The implications of these results for the treatment of malignant tumours by radiotherapy are briefly discussed.

Alpha Particles↗

A possible combination of hypoxic cell sensitizer with an oxic protector: implications for radiotherapy.

This paper discusses the results of experiments using γ-rays and a hypoxic sensitizer metronidazole (MET) and also a well-known protector, mercaptoethylamine (MEA), individually and in combination, on the survival of the yeast S. cerevisiae BZ 34. MET (5mM) gave a hypoxic enhancement ratio (ER) of 1·3. MEA (5mM, 10mM) gave a dose-modifying factor (DMF) of 1·9 and 2·3 respectively for euoxic cells. However, the DMFs for hypoxic cells were 1·0 and 1·1 for 5 and 10mM concentrations of MEA. A combination of 5mM MEA and 5mM MET gave a DMF of 2·0 for euoxic cells and the ER remained at 1·3 for hypoxic cells. The "effective" oxygen enhancement ratios were 2·3 and 1·7 for the control and the sensitizer respectively. In the combination this value was equal to or even slightly less than 1. All DMF, ER and OER values were derived from D(0) values of the survival curves. The values based on 10% survival are almost equal to those derived from D(0) values. All the survival curves gave the same extrapolation number, showing that the chemicals individually or in combination were truly dose-modifying.These results indicate that protectors such as MEA could be preferentially protecting euoxic cells, and that combining such "oxic protectors" with a hypoxic sensitizer could result in protecting euoxic cells while the sensitization of hypoxic cells was not much reduced. The implications of our results for radiotherapy are discussed. It appears that the use of nontoxic oxic protectors may be a useful adjuvant in overcoming the hypoxic-cell problem in radiotherapy.

Dose-Response Relationship, Drug↗