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A Guide to the Russian Academy of Sciences - University of Texas ...

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We proposed <strong>to</strong> demonstrate <strong>the</strong> increased permeability <strong>of</strong> malarial-infected<br />

erythrocytes <strong>to</strong> ODN and <strong>to</strong> investigate <strong>the</strong> antimalarial activities <strong>of</strong> various ODNderivatives.<br />

7. Sec<strong>to</strong>r <strong>of</strong> Medicine Genetics.<br />

Staff:<br />

Anna E. Dikalova, Ph.D., Head <strong>of</strong> <strong>the</strong> Sec<strong>to</strong>r<br />

Aleksander M. Gonchar, Ph.D.<br />

Irina G. Shabalina, Ph.D.<br />

Larisa N. Kudryashova<br />

Julija V. Ablaeva<br />

Sergey I. Dikalov, Ph.D.<br />

Subjects <strong>of</strong> Research:<br />

Molecular mechanisms <strong>of</strong> <strong>the</strong> development <strong>of</strong> deseases involving enchanced oxygen<br />

radical generation. The role <strong>of</strong> free radicals in <strong>the</strong> increased mutation rate in animal<br />

and plant cells. Molecular basis <strong>of</strong> somaclonal variation.<br />

General Results 1993-1995:<br />

By selecting and inbreeding Wistar rats which are sensitive (S) or<br />

resistant (R) <strong>to</strong> <strong>the</strong> catarac<strong>to</strong>genic effect <strong>of</strong> galac<strong>to</strong>se <strong>the</strong> S and R rat<br />

strains were developed. Intense generation <strong>of</strong> oxygen radicals and<br />

enhanced lipid peroxidation were revealed in <strong>the</strong> liver and<br />

myocardium <strong>of</strong> <strong>the</strong> S rats. Data were obtained supporting <strong>the</strong><br />

hypo<strong>the</strong>sis that enhanced generation <strong>of</strong> OH-radicals in <strong>the</strong> S rat cells<br />

is due <strong>to</strong> <strong>the</strong> oxidation and au<strong>to</strong>oxidation <strong>of</strong> <strong>the</strong> increased amounts<br />

<strong>of</strong> monosaccharides intensively transported in<strong>to</strong> <strong>the</strong> rat cells.<br />

Numerous DNA rearrangements were found in <strong>the</strong> S rat genomes.<br />

Decreased oxidative phosphorilation and <strong>the</strong> lower respira<strong>to</strong>ry<br />

control ratio were found in liver mi<strong>to</strong>chondria <strong>of</strong> S rat. Formation <strong>of</strong><br />

protein carbonyl groups and membrane fluidity were increased. SOD<br />

and catalase activity were decreased. Tumors, premature aging (low<br />

fecundity, growth retardation and short life-span), cataracts,<br />

cardiomyopathy-like changes in <strong>the</strong> myocardium, scoliosis are<br />

characteristic <strong>of</strong> <strong>the</strong> S rats.<br />

Preliminary data demonstrated that <strong>the</strong>re are groups <strong>of</strong> patients with<br />

scoliosis, cardiomyopathy, a<strong>the</strong>rosclerosis in families predisposed<br />

<strong>to</strong> <strong>the</strong>se diseases which are characterized by a very intense hexose<br />

transport in<strong>to</strong> cells, enhanced free radical generation and lipid<br />

peroxidation.<br />

The high mutation rate in <strong>the</strong> genome <strong>of</strong> <strong>the</strong> plant cells which are grown in<br />

cell suspension or in tissue culture is known as somaclonal<br />

variation. Although extensive documentation <strong>of</strong> this phenomenon is<br />

available in numerous plant species, <strong>the</strong> existing data on this subject<br />

do not allow <strong>to</strong> make unambiguous conclusion about <strong>the</strong> nature <strong>of</strong><br />

somaclonal variation. We advanced <strong>the</strong> suggestion that culturing <strong>of</strong><br />

plant cells in vitro are stressful conditions which may result in <strong>the</strong><br />

hyperproduction <strong>of</strong> oxygen free radicals which in turn react with<br />

DNA and cause <strong>the</strong> mutations. If it is so, we may regulate <strong>the</strong><br />

mutation process using in medium <strong>the</strong> agents stimulating or<br />

1010

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