UV- and MMS-induced mutagenesis of lambdaO(am)8 phage under nonpermissive conditions for phage DNA replication.

Mutagenesis in Escherichia coli, a subject of many years of study is considered to be related to DNA replication. DNA lesions nonrepaired by the error-free nucleotide excision repair (NER), base excision repair (BER) and recombination repair (RR), stop replication at the fork. Reinitiation needs translesion synthesis (TLS) by DNA polymerase V (UmuC), which in the presence of accessory proteins, UmuD', RecA and ssDNA-binding protein (SSB), has an ability to bypass the lesion with high mutagenicity.

The isfA mutation specifically inhibits the SOS-dependent mutagenic pathway and does not selectively affect any particular base substitution.

We have previously described a new mutation in Escherichia coli, isfA, which causes inhibition of SOS mutagenesis (UV-induced in rec+ and spontaneous in recA730 strains) and several SOS-dependent phenomena. Antimutagenic activity of the isfA mutation in the recA730 strain was shown to be related to inhibition of processing of UmuD to UmuD' by RecA* coprotease. In the present study we have analysed the specificity of the antimutagenic activity of the isfA mutation by employing F' plasmids carrying a set of mutant lacZ genes that can individually detect two types of transitions and four types of transversions.

[Vascular ischemic dementia].

Observations are reported of the course and other interrelations between clinical pattern and computer tomography results in 36 patients with vascular ischaemic dementia. Attention is called to the frequency of transient dementia-like disturbances following stroke and to the importance of the middle gyrus of the left frontal lobe in the development of dementia manifestations. In cases with slow progression of dementia symptoms and only scant neurological signs not infrequently long-standing improvement or even complete remission of dementia symptoms occur which sets them apart from mixed forms of dementia.

The isfA mutation inhibits mutator activity and processing of UmuD protein in Escherichia coli recA730 strains.

Further studies on the isfA mutation responsible for anti-SOS and antimutagenic activities in Escherichia coli are described. We have previously shown that the isfA mutation inhibits mutagenesis and other SOS-dependent phenomena, possibly by interfering with RecA coprotease activity. The isfA mutation has now been demonstrated also to suppress mutator activity in E.

A new mutation in Escherichia coli K12, isfA, which is responsible for inhibition of SOS functions.

A new mutation in Escherichia coli K12, isfA, is described, which causes inhibition of SOS functions. The mutation, discovered in a delta polA+ mutant, is responsible for inhibition of several phenomena related to the SOS response in polA+ strains: UV- and methyl methanesulfonate-induced mutagenesis, resumption of DNA replication in UV-irradiated cells, cell filamentation, prophage induction and increase in UV sensitivity. The isfA mutation also significantly reduces UV-induced expression of beta-galactosidase from recA::lacZ and umuC'::lacZ fusions.

[Cigarette smoking and alcohol abuse effects on stroke development].

Cigarette smoking, alcohol abuse and stroke--the material consisted of 272 patients (169 men and 103) women aged between 25-65 years. There were 221 patients with ischemic stroke and 51 patients with haemorrhagic stroke. The control group consisted of 400 healthy subject of the same age and sex.

[Subacute hypoglycemic encephalopathy: a case report].

A 63-year-old woman with long lasting diabetes, irregularly nourished and treated with oral antidiabetic drugs, developed hyperkinetic movements in the upper and lower extremities and facial muscles, as well as some disturbances of consciousness. The EEG showed generalized slowing of bioelectrical activity, serum glucose level was 69 mg%. Nevertheless after the antidiabetic drugs were withdrawn and the meals regulated, a normalization of the clinical picture and the EEG was observed.

Involvement of DNA lesions and SOS functions in 5-bromouracil-induced mutagenesis.

Mutagenesis resulting from incorporation of 5-bromouracil (BU) in the DNA of E. coli K12 proceeds largely (approximately 80%) via misrepair of the lesions resulting from incorporation of the analogue. The premutational lesions are due principally to dehalogenation of incorporated BU residues, leading to formation of uracil residues, and removal of these by uracil-DNA glycosylase with formation of apyrimidinic sites.

Mutagenesis induced by 5-bromouracil and methyl methane sulfonate: role of DNA polymerase I.

A polA1 mutation in the DNA polymerase I gene of E. coli results in a drastic reduction of the frequency of mutagenesis induced by 5-bromo-2'-deoxyuridine (BUdR). Comparisons of the effect of a polA1 mutation on mutagenesis induced by methyl methane sulfonate (MMS), ultraviolet irradiation (UV) and 2-aminopurine (2-AP) demonstrated that a similar effect of a polA1 mutation is observed with MMS.

Induction of SOS functions in Escherichia coli by lesions resulting from incorporation of 5-bromouracil into DNA.

Lesions induced by 5-bromouracil (BU), after its incorporation into DNA, led to effective induction of prophage lambda and W reactivation (or BU reactivation). Prophage induction due to incorporated BU occurred only with the wild-type prophage, and not for the lambda c1857 mutant with a thermosensitive repressor. Antipain, a protease inhibitor, inhibited wild-type prophage induction 70-90%.

Identification of uracil as a major lesion in E. coli DNA following the incorporation of 5-bromouracil, and some of the accompanying effects.

Cultivation of E. coli cells in the presence of 5-bromodeoxyuridine (BUdR) leads to formation of lesions in the cellular DNA which affect its secondary structure, as reflected by changes in temperature profiles. Such DNA contains single-stranded regions susceptible to endonuclease S1.

Evidence implying DNA polymerase beta function in excision repair.

Comparison was made of the ability of calf thymus DNA polymerases alpha and beta to replicate the following templates: native E. coli CR-34 DNA (T-DNA), calf thymus DNA activated by DNase I (act.DNA), BU-DNA (from E.

Genetic evidence for the nature, and excision repair, of DNA lesions resulting from incorporation of 5-bromouracil.

Escherichia coli mutants defective in DNA uracil N-glycosidase (ung-) or endonuclease VI active against apurinic/apyrimidinic sites in DNA (xthA-) exhibit enhanced sensitivity towards 5-bromodeoxyuridine relative to the wild type strain, pointing to involvement of these enzymes in repair of bromouracil-induced lesions in DNA. Mutants defective in DNA polymerase I, either in polymerizing activity (polAl-) or (5' leads to 3')-exonuclease activity (polA107-) exhibit unusually high sensitivity (including marked lethality) in the presence of 5-bromodeoxyuridine. The results indicate that DNA polymerase I, and its associated (5'--3')-exonuclease activity, are involved in repair of bromouracil-induced lesions and are not readily replaced, if at all, by DNA polymerases II and III.

5-Ethyldeoxyuridine, a thymidine analog: photochemical transformation.

Irradiation at 254 millimicrons transforms 5-ethyldeoxyuridine to deoxyuridine by way of photohydration of the 5,6 bond and elimination of ethanol. At wavelengths to the red side of 265 millimicrons, photodimerization is the principal reaction, with a pronounced oxygen effect. The results are related to the photochemistry of thymidine and of bacteriophages containing incorporated 5-ethyluracil in place of thymine.