Weakening of the ultraviolet ray-induced unscheduled DNA synthesis in human lymphocytes in extreme old age

The intensity of unscheduled DNA synthesis was studied in UV-irradiated (10--15 J/m2) peripheral blood lymphocytes of 80--90 years old persons. In these extreme old age persons, reparative DNA synthesis was found sufficiently reduced in comparison with that in middle aged (20--43 years old) ones. The role of DNA repair processes in ageing is under discussion.     

Identification of elements responsible for regulation of keratinocyte growth factor gene by steroid hormones and 1,25-dihydroxyvitamin D3

Data are provided on the up-regulation of keratinocyte growth factor gene (kgf) at mRNA and protein level in prostate cancer cells (LNCaP) stimulated by 1,25-dihydroxy-vitamin D3 and 17-beta-estradiol (E2). The computer analysis of the 5-flanking region of kgf gene using different software and databases (TESS, TRANSFAC etc.) enabled us to identify some potential elements responsible for binding the nuclear receptors of vitamin D3, E2, and some other steroid hormones.     

Discrimination of heterozygote currency of ataxia-telangiectasia by indirect immunofluorescent analysis

The qualitative differences in P53 protein stabilization after ionizing irradiation in different doses were found in cells of members of ataxia-telangiectasia (AT) family--proband AT6SP, her sister AT(S)6SP and father AT(F)6SP. The method of indirect immunofluorescence with confocal microscopy was used.     

The atypical of Werner syndrome: effect of laminopathy

A case of adult progeria has been described. During detailed studies of the cells from this patient the nuclear lamina and cytoskeleton aberrations were detected. It has been suggested that this case is an atypical form of Werner syndrome with laminopathy--not the WRN helicase-nuclease defect.     

Features of the radiosensitivity of cells from ataxia-telangiectasia patients]

Cell survival, single and double DNA strand breaks formation and removal, spontaneous and induced chromosome aberrations and sister chromatid exchange (SCE) levels in gamma-irradiated cells of patients with ataxia-telangiectasia (AT) were studied. Except SCE all of the above indexes of AT cells sensitivity, were higher, than in normal human cells, but lower, than it is commonly characteristic of AT cells in literature. A conclusion is that the analysed AT cells belong to the AT-variant form. Possible mechanisms of high radiosensitivity of AT cells, accompanied by radioresistance of DNA replication, are discussed. The authors suppose that the DNA repair defect in AT cells is not primary.     

Gene structure,transcripts and calciotropic effects of the PTH family of peptides in <Emphasis Type="Italic">Xenopus</Emphasis> and chicken

Background  

Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34) and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L) was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken.     

Repair of DNA damaged by methylmethane sulfonate in normal human lymphocytes and in xeroderma pigmentosum

Methylmethanesulphonate has been shown to stimulate an intensive unscheduled DNA synthesis in lymphocytes derived from normal donors as well as in those from patients with xeroderma pigmentosum of the classical form. Somewhat less intensive unscheduled DNA synthesis was observed in cells of a patient suffering from xeroderma pigmentosum. In the case of XPII unscheduled DNA synthesis was greatly reduced which supports the peculiarity of this form of xeroderma pigmentosum.     

Spontaneous and induced sister chromatid exchanges in the blood lymphocytes of healthy persons and of xeroderma pigmentosum patients exposed to the inhibitors of DNA repair and replication caffeine, 3-methoxybenzamide and novobiocin

The frequency of sister chromatid exchanges (SCEs), both spontaneous and induced by UV-light, X-rays, mitomycin C and ethylmetansulphonate (EMS), has been investigated in cultured human peripheral blood lymphocytes. Besides, frequency of spontaneous and induced SCEs was studied under the action of the inhibitors of topoisomerase II, polymerase poly(ADP-ribose), and DNA repair, i. e. novobiocin, 3-metoxybenzamide, and caffeine, respectively. It is shown that the base-line SCEs in lymphocytes of the patient with xeroderma pigmentosum II (XP2LE) is dramatically higher compared to that in normal and pigmented xerodermoid cells (XP3LE). The above inhibitors of DNA synthesis and repair enhance the rate of spontaneous SCEs in normal, XP2LE and XP3LE cells. UV-, X-ray and chemical mutagens induced an increased frequency of SCEs in these cells. Simultaneous treatment with mutagenes and inhibitors of DNA synthesis and DNA repair enhanced the rate of SCEs in lymphocytes of healthy donors and in the XP3LE patient. The frequency of the XP2LE cells. Novobiocin, 3-MBA and caffeine significantly decreased the frequency of SCEs in mitomycin C- and EMS-treated XP2LE lymphocyte, which nevertheless was much higher than that in normal cells treated with the same agents.     

Number of chromosome aberrations induced by chemical carcinogens in the cells of patients with 2 forms of xeroderma pigmentosum

A study was made of the effects of a chemical mutagen of the "gamma-type"--methylmethansulfonate (MMS) and of mutagen of the "UV-type"--4-nitroquinolin-1-oxide (NQO) and 7-brommethylbenz(alpha)antracen (BMBA) exerted on chromosome aberration frequency in lymphocytes of patients with classical Xeroderma pigmentosum and with a so-called form II of the disease on different stages of the cell cycle. Mutagens were added to PHA stimulated lymphocyte cultures every 3 hours, simultaneously with pulse 3H-thymidine labelling, to fix the stage of the cell cycle at the moment of treatment. NQO and BMBA treatments were found to increase the frequency of chromosome aberrations in classical XP cells, whereas MMS was not found to. In the XP II cells, defective in repair of both UV and gamma damaged DNA, chromosome aberrations yield is higher than in normal cells after all the three mutagens treatment. The data obtained show the correlation between DNA repair and chromosome aberrations yield.