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Biomedical subjects

F Berends

Publications and source records attributed to F Berends.

48 records · Page 3Linked to original sources
PubMed1981

The mutagenicity of isoniazid in Salmonella and its effects on DNA repair and synthesis in human fibroblasts.

A commercial sample of the tuberculostatic drug isoniazid (INH) was found to have a weak mutagenic activity towards Salmonella typhimurium strains TA100 and TA1535. The addition of a rat or mouse liver homogenate to the test system decreased the mutagenic effect of INH. Hydrazine, an impurity of the INH sample, was also weakly mutagenic in strains TA100 and TA1535, but not in the extent that could account for the mutagenicity of the INH sample. An inhibition of DNA synthesis in human fibroblasts was observed for INH, this effect being potentiated by the addition of manganese to the test system. There was no induction of unscheduled DNA synthesis in human cells by INH except in the presence of manganese.

Cells, Cultured↗
PubMed1980

Repair of damage by ultraviolet radiation in xeroderma pigmentosum cell strains of complementation groups E and F.

The xeroderma pigmentosum fibroblast strains XP2RO, complementation group E, and XP23OS, group F, were compared with normal human primary fibroblasts with regard to repair of damage induced by 254-nm UV. In XP2RO cells, repair DNA synthesis, measured by autoradiography (unscheduled DNA synthesis = UDS), was about 50% of the value found in normal human cells. In these cells also the removal of UV-induced sites recognized by a specific UV-endonuclease proceeds at a reduced rate. By having BUdR incorporated into the repaired regions, followed by the induction of breaks in these patches by 313-nm UV, it was shown that the reduced repair synthesis is not caused by a shorter length of the repair regions in XP2RO, but is solely due to a reduction in the number of sites removed by excision repair. In XP23OS a discrepancy was observed between the level of UDS, which was about 10% of the normal value, and other repair-dependent properties such as UV survival, host-cell reactivation and removal of UV-endonuclease-susceptible sites, which were less reduced than could be expected from the UDS level. However, when UDS was followed over a longer period than the 2 or 3 h normally used in UDS analysis, it appeared that in XP23OS cells, the rate of UDS remained constant whereas the rate decreased in normal control cells. Consequently, the residual level of UDS varies with the period over which it is studied.

Bromodeoxyuridine↗
PubMedDate not supplied

DNA damage metabolism and aging.

As a result of permanent exposure to low levels of various endogenous and exogenous genotoxic agents, large numbers of lesions are continuously induced in the DNA of cells of living organisms. Such lesions could lead to dysfunction of cells and tissues, and they might well be the underlying cause of the age-related reduction of homeostatic capacity and the increased incidence of cancer and other diseases of old age. The rate of damage induction as well as the persistence of the lesions depends on the activity, efficiency and reliability of a wide variety of molecular defense systems. However, a certain degree of imperfection seems to be a general characteristic of most of these defense systems and this could lead to a gradual accumulation of DNA alterations during aging. Even when the original lesions are quickly removed, they can still lead to secondary changes in the DNA, such as DNA-sequence changes and changes in gene expression. This process would be accelerated in case of the occurrence of an age-related decline in the efficiency of these molecular defense systems. This review deals with the present knowledge on the occurrence of 'spontaneous' DNA damage in aging organisms, its potential sources, the influence of preventive and processive cellular defense mechanisms and its consequences in terms of DNA-sequence changes, DNA conformational and configurational changes and changes in gene expression. In general, it can be concluded from the data discussed here that, in spite of a number of discrepancies and conflicting results, an age-related accumulation of DNA alterations occurs at all levels, e.g., chemical structure, DNA-sequence organization and gene expression.

Aging↗