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Biomedical subjects

V I Korogodin

Publications and source records attributed to V I Korogodin.

At least 19 recordsLinked to original sources

Radiosensitivity of haplont yeast cells irradiated with sparsely and densely ionizing radiations.

Five haploid and three diploid yeast strains of various species (Yarrowia lipolytica, Pichia pinus and Pichia guilliermondii) were irradiated with alpha-particles from 239Pu and gamma-rays from 137Cs or 60Co in the stationary phase of growth. A common feature of these species is that they exhibit a haploid state as a normal vegetative state in natural conditions. It was shown that the transition from the haploid to the diploid state is not accompanied by increased radioresistance, and diploid strains were unable to perform liquid-holding recovery. The absence of diploid-specific recovery in diploid strains was also supported by the fact that the RBE of alpha-particles was almost identical for haploid and the corresponding diploid strains being much smaller than that observed in typical wild-type diploid strains capable of diploid-specific recovery. The results suggest that haplont yeast may have evolved to diplont yeast via the development of a specific repair system conferring specific resistance in the diploid state.

Alpha Particles↗

[Characteristics of spontaneous mutagenesis in haploid yeast].

The dynamics of appearance of spontaneous revertants was studied in haploid strains of Saccharomyces cerevisiae, auxotrophic for adenine or leucine. Mathematic models of this process were used. It was confirmed that in the case of adenine auxotrophs, an increase in the number of revertants, depending on decreasing adenine content, was caused by a change in mutation rate of the ade2 gene. For leucine auxotrophs, a similar phenomenon was determined by an increase in the rate of appearance of Leu+ revertants due to a decrease in size of initial auxotrophic cell colonies. Alteration in leucine content in the medium from 3 to 300 mg/l did not lead to a change in the reversion rate for the leu2 gene. The heterogeneity of revertants detected at different times was described.

Adenine↗

Characteristics of spontaneous revertants in haploid yeast.

The appearance dynamics of spontaneous revertants in adenine- or leucine-auxotrophic haploid Saccharomyces cerevisiae strains has been studied using mathematical simulation methods. In the case of adenine auxotrophs an increase in the number of revertants with decreasing metabolite content is found to result mainly from increasing the rate of intragenic suppressor mutations. In the case of leucine auxotrophs revertants result from increasing the appearance of mutants formed at similar rates under different cultivation conditions. In the latter case the appearance of mutant colonies increases with decreasing size of colonies of the initial auxotrophic cells. The last can simulate so-called adaptive mutagenesis. The heterogeneity of revertants appearing in different time periods is described.

Culture Media↗

The study of post-irradiation recovery of yeast: the 'premolecular period'.

Recovery of yeast cells after exposure to ionizing radiation was discovered in 1957. During the following decade, i.e., in the 'premolecular period' of studying this phenomenon, its basic features including dependence on cell ploidy, cellular energy exchange and radiation linear energy transfer (LET) were determined and a mathematical model of recovery was proposed. In addition, DNA double-strand breaks were shown to be the damage causing death of irradiated haploid and diploid cells. The results of these investigations led to the formulation of the concept that the ability of a cell to repair genetic damage was of universal biological importance.

Cell Death↗

On the dependence of spontaneous mutation rates on the functional state of genes.

Spontaneous mutation of some genes was studied in haploid adenine and leucine auxotrophic yeast Saccharomyces. It was shown that a decrease in the amount of adenine (from 500 to 0 mg l-1) or leucine (from 300 to 0.3 mg l-1) in the medium, simultaneously with the transition from repression to derepression of the biosynthesis of these metabolites, resulted in a 15- to 150-fold increase in the reversion rate of genes ade 2 and leu2, respectively, for different strains. At the same time the mutation rate of suppressor genes varied relatively little (up to five-fold), and that of gene lys did not change at all. It was also demonstrated (on gene leu2) that the mutation rate is determined by the composition of the nutrient medium at the time of the S-phase of the cell cycle and it does not depend on the cultivation conditions during the presynthetic period. We discuss the hypothesis that derepressed genes mutate with a significantly higher rate than genes in the repressed state.

Adenine↗

Mathematical model of Ehrlich ascites tumor growth from in vitro treated cells.

A mathematical model is proposed describing the dependence of lethality and average life-span in mice on the number of Ehrlich ascites tumor (EAT) cells inoculated both intact or treated in vitro with various agents. Particularly, the effect of ionizing radiation is discussed, and the effect of combined action of two agents is also considered.

Animals↗

Lethal effect of glucose load on malignant cells.

Ehrlich ascites tumor (EAT) cells were treated by glucose load under anoxic conditions (for 15 or 60 min) and/or by gamma-radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells by glucose load in anoxia and by gamma-radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached.

Animals↗

[The proof of real increase in the frequency of reverse mutations in haploid yeasts in media with decreased adenine content].

It has been shown by the direct experiment in the haploid yeast Saccharomyces cerevisiae, strain p192 (a ade2-192), that, if cultivated in the solid media containing 1 and 10 mg/l of adenine, the reversion frequencies (5.6 X 10(-8) and 0.82 X 10(-8), respectively) do not depend on the number of cells (from 10(2) to 10(7)) in colonies growing on either medium. This means that the difference in the reversion frequencies mentioned is not connected with the "selection effect" and is only caused by the varying initial content of adenine in the medium. A method combining the technique of ordered plating and the use of nuclear filters is recommended for the study of mutagenesis in microorganisms.

Adenine↗

[Relation between the frequency of various types of reverse mutations in yeasts auxotrophic for adenine and the adenine content of the medium].

As shown in the haploid yeast Saccharomyces cerevisiae, the strain 769-p192-15B-n4 (a ade2-192 lys5-3), the rates of reversion to adenine prototrophy are 0.36 X 10(-8), 1.7 X 10(-8) and 2.7 X 10(-8), when the medium contains 100, 10 and 1 mg/l adenine, respectively. Two types of revertants were taken into account: those prototrophic both for adenine and lysine, i. e. suppressors, and those prototrophic for adenine only, most of them being locus revertants. The proportion of locus revertants at 100, 10 and 1 mg/l adenine does not exceed 2, 25 and 41%, respectively. It is assumed that excess adenine (100 mg/l) suppresses the activity of the genes controlling its synthesis, including the mutant ade2 gene. A hypothesis is forwarded, according to which the genes being in the "active" state mutate significantly more frequently than "not working" genes.

Adenine↗

[Lethal effect of glucose load on tumor cells in hypoxia].

The in vitro treatment of the Ehrlich ascites tumour (EAT) cells with glucose for 15 and 60 min under hypoxic conditions leads to a decrease in their survival by a factor of 10(2) and 10(4). Glucose load is ineffective under normal oxygenation. The mass destruction of EAT cells under the influence of glucose takes place within the first 24 hours in the interphase. The lethal effect of different pH values on EAT cells is independent of the way by which the given pH value was reached (glucose load or phosphate buffer). The same values of pH lead to the same effect on EAT cells. The lethal effect markedly increased when the value of pH was lower than 5.6. It is concluded that the lethal effect of the glucose load is due to self acidification of EAT cells.

Animals↗

[Effect of the adenine level of a culture medium on the frequency of revertants in haploid yeasts].

The frequency of reversion from adenine auxotrophy in the yeast Saccharomyces cerevisiae increases with the decrease of adenine concentration in the medium: for the 8PG-59 strain (a ade2-192 rad2) the reversion frequency is 1.7 X 10(-8), 3.2 X 10(-6) and 1.8 X 10(-5) per cell division, the initial adenine concentrations being 10, 1 and 0.1 mg/l, respectively. An increase of the reversion frequency with the culture age in the stationary phase of growth is demonstrated using an improved method of registration of revertants, with the initial concentration of 0.1 mg/l of adenine in the medium. The reversion frequency was 9.1 X 10(-7) on the 7th day, 1.8 X 10(-6) on the 10th day and 1.8 X 10(-5) on the 14th day.

Adenine↗

Influence of Cosmos 368 space flight conditions on radiation effects in yeasts, hydrogen bacteria and seeds of lettuce and pea.

Radiobiological studies have been carried out on board the Cosmos 368 satellite, launched on 8 October 1970 and returning to earth on 14 October 1970. Yeast diploid cells Saccharomyces ellipsoides, Megri strain 139-B, haploid cells Zygosaccharomyces Baili, hydrogen bacteria Hydrogenomonas eutropha, strain Z-1, Berlin variety lettuce seeds and Capital variety pea seeds were used in these experiments. The biological specimens were irradiated with gamma-rays at dose rates of 71.8 and 6.7 rad d-1 suring the packaging of containers and after returning the samples to the laboratory. It was found that both on pre-radiation and post-radiation exposure space flight factors did not greatly influence radiobiological effects.

Cosmic Radiation↗