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We have carried out experiments to study the possible induction of an adaptive response in cultured bovine and rabbit lymphocytes conditioned with subtoxic doses of hydrogen peroxide after stimulation and subsequently challenged with 1 Gy of X-rays. Peroxide treatment was given at different doses 48 h after the addition of PHA to stimulate the cells. A protective effect of pre-exposure to H ...
Non-genotoxic carcinogens cause cancer without damaging the DNA. Peroxisome proliferators (PPs) are a class of potent rodent non-genotoxic hepatocarcinogens that may act by perturbing hepatocyte growth regulation. Previously, we have shown that although cultured rat hepatocytes degenerate rapidly in culture, their survival can be reversibly maintained by the PP nafenopin. This prolonged survival...
An inbred mouse strain HLG shows a high incidence of gastroschisis after X-ray exposure to the zygotes. About 11% of the fetuses display this malformation after irradiation with 1 Gy. The C57BL-strain does not show the increased frequency of gastroschisis after radiation-exposure to the zygotes. The genetic background of this malformation was investigated in a backcross of HLG C57BL females...
The aim of this article is to study the relationship between GSTM1 polymorphism and colon cancer and to compare the chromosomal breakage induced by mutagen in a colon cancer group and healthy controls. Using PCR to identify the GSTM1 genotype, we found the frequency of GSTM1 - in colon cancer (n = 19) and control group (n = 23) was 36.8% and 26.1%, respectively (p > 0.05, χ 2 -test)...
The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelenghts (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo andHSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely...
An optical biosensor was used to monitor interactions between the Escherichia coli DNA mismatch repair molecule MutS and various immobilized oligonucleotides. While associating poorly with single-stranded DNA, MutS was capable of rapid association/dissociation from homoduplex DNA. The interaction of MutS with oligonucleotide 30-mers containing single site mismatches demonstrated that during the...
The effects of 21 amino acids on sister-chromatid exchanges (SCEs) in human lymphocytes were investigated. Addition of each of the 21 amino acids, originally in a composition of the culture medium RPMI 1640, at three different concentrations (10 μg/ml, 50 μg/ml and 100 μg/ml) caused a dose-independent increase in SCE frequency. The results indicated that amino acids, although indispensable for cells...
2,3-Diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP) are products generated from oxidative-type phenylenediamine hair dyes and are also present in pesticide formulations as contaminants. Earlier studies demonstrated that DAP and AHP were mutagenic in Salmonella typhimurium strains after mammalian microsomal activation. Plant systems can activate structurally similar arylamines. S. typhimurium...
To explore further the origin of spontaneous mutations recovered with the Big Blue transgenic mouse mutagenesis assay, the spectrum of ex vivo mutations from pinpoint mutant plaques was determined and compared with the spectrum of putatively mouse-derived mutations from circular, mutant plaques. The entire lacI gene and lacZ operator region from 62 pinpoint blue plaques was sequenced. The observed...
In experiments using yeast without addition of an external metabolic activation system, (E)-5-(2-bromovinyl)-2 -deoxyuridine (BVDU) was co-mutagenic and showed an insignificant anti-recombinogenic effect in combination with triethylene melamine (TEM). In the presence of activating S9-mix, the anti-recombinogenicity and co-mutagenicity could clearly be seen. At higher concentrations the co-mutagenic...
Cytogenetic damage and cytotoxicity produced by a range of acute treatments with bleomycin (BLM) were investigated in three B-lymphoblastoid cell lines: EM-OC, PA-AT and CP-NC; established from heterozygous, and homozygous, ataxia telangiectasia (AT) and normal donors, respectively. The following endpoints were studied: (1) the maximum (initial) yields of different classes of chromosomal aberrations...
Pretreatment with sublethal doses of X-rays induced an adaptive response in Vibrio cholerae cells as indicated by their greater resistance to the subsequent challenging doses of X-irradiation. The adaptive response was maximum following a pre-exposure dose of 1.7 Gy X-rays and an optimum incubation period of 40 min at 37°C. Pre-exposure to a sublethal dose of 1.7 Gy X-rays made the Vibrio cholerae...
The Rat2 TM cell line carries 50-70 stably integrated copies per cell of a λ/lacI shuttle vector as a target for mutagenicity testing. Rat2 TM cells were exposed to 1 and 10 μg/ml of 7,12-dimethylbenz[a]anthracene (DMBA) for 24 h at 37°C in the presence of primary rat hepatocytes, and grown to confluence. The shuttle vector was rescued from untreated and mutagen-treated...
lacZ gene mutations in the transgenic Muta TM Mmouse can be detected by two different selection systems. While mutant frequencies recovered by phenyl-β-d-galactoside (P-gal) selection are comparable with those obtained using 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside (X-gal) as substrate for β-galactosidase, there may still be differences at the molecular level in the mutations...
The mechanisms by which an electromagnetic field (EMF) influences biological material are poorly understood. One potentially important model suggests that a magnetic field can stabilize free radicals in such a way as to permit their dispersement rather than their return to the ground state (Okazaki et al., 1988, Scaiano, 1995). We have tested this hypothesis by examining mutagenesis in the E. coli...
Similarities between structures in SAR models derived from different data bases, termed structural overlap , can be used for determining mechanistic similarities, e.g., mutagenicity vs. carcinogenicity. However, the structural overlap may be affected by the proportion of common chemicals in the data bases, termed chemical overlap . In order to refine our ability to determine mechanistic similarities,...
Frequencies of intra-chromosomal exchanges (pericentric inversions and centric rings) and inter-chromosomal exchanges (dicentrics and translocations) in X-irradiated (2.5 Gy) human lymphocytes have been estimated. To detect these events we employed FISH (fluorescence in situ hybridization) technique and arm specific painting probes for chromosomes #1 and #3. The ratio between centric rings and pericentric...
The basis for sex-specific differences in chemically-induced and age-related aneuploidy of mammalian germ cells is still unknown. We have analysed the maturation of isolated mouse oocytes to characterize the mechanisms underlying drug-induced aneuploidy produced by two compounds, chloral hydrate (CH) and diazepam (DZ). When administered in vivo both drugs increase hyperploidy in male but not in...
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