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We have utilized (CHO)-PL61 cells to characterize the mutations produced in mammalian cells by exogenous treatment with the nucleoside 5-hydroxymethyl-2 -deoxyuridine (hmdUrd). HmdUrd is incorporated into DNA as a thymidine analogue and is removed by the repair enzyme hmUra-DNA glycosylase. PL61 cells are hprt - and contain adjacent single copies of the Escherichia coli gpt and neo genes...
Mice can survive lethal doses of ionizing radiation if deoxyribonucleosides or highly polymerized salmon sperm DNA (Sigma) are administered 30 min to 24 h post-irradiation. DNA is more effective than deoxyribonucleosides in increasing the survival frequency. At supralethal exposures of y-irradiation, Deoxyribonucleosides and DNA are equally effective in reversing radiation damage which otherwise...
Benzene is a human carcinogen present naturally in petroleum and gasoline. For the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity, benzene and its principal metabolites, phenol, catechol and hydroquinone were examined for their ability to induce cell transformation and genotoxic effects using the same mammalian cells in culture. Each of the four compounds induced morphological...
Human bone marrow mononuclear cells were isolated by density gradient centrifugation and irradiated with a 137 Cs source. The extent of irradiation-induced single-strand breaks (SSBs) and alkali labile sites as well as their repair was investigated by using the alkaline single-cell gel electrophoresis (SCGE) technique, or comet assay. A dose-dependent increase in the length of...
The mitostatic action of the commonly used fungicide methyl 2-benzimidazolecarbamate (MBC) was evaluated in primary cultures of human ovarian granulosa cells with respect to the organization and stability of spindle microtubules and mitotic centrosomes. MBC caused metaphase arrest and abnormal chromosome organization following a 3-15 h treatment at a concentration of 30 μM. While microtubules were...
The functions of metallothioneins (MTs) have been debated for at least a decade. Because it seems unlikely that they evolved only to protect cells against exogenous heavy metals, it has been suggested that MTs have roles in scavenging reactive intermediates, controlling zinc and copper homeostasis, and controlling transfer of zinc to transcription factors and other proteins. Previously, we demonstrated...
Incubation of both rat and mouse hepatocytes with 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in vitro resulted in a dose-dependent increase in unscheduled DNA synthesis (UDS) at sub-cytotoxic concentrations (1-10 μM MX; 20 h incubation). Depletion of glutathione stores by pre-treatment of rat hepatocytes with buthionine sulfoximine did not result in a significant increase in UDS produced...
In order to estimate possible mutagenic and/or carcinogenic activity of electromagnetic fields, wing spot tests were performed in Drosophila melanogaster. A DNA repair defective mutation mei-41 D5 was introduced into the conventionalmwh/flr test system to enhance mutant spot frequency. Third instar larvae were exposed to a 5-Tesla static magnetic field for 24 h, and after molting, wings...
Clastogenic factors (CFs), as they were described previously in accidentally or therapeutically irradiated persons, in A-bomb survivors and in liquidators of the Chernobyl nuclear power plant, were also detected in the plasma of Chernobyl-exposed children. A high percentage of plasma ultrafiltrates from 170 children, immigrated to Israel in 1990, exerted clastogenic effects in test cultures set up...
RecA730 belongs to a class of mutant RecA protein that is often referred to as RecA * , since it is constitutively activated for coprotease functions in the absence of exogenous DNA-damage. Escherichia coli strains carrying recA730 (or otherrecA * alleles) exhibit dramatic increases in SOS-dependent spontaneous mutator activity. We have analyzed the specificity of this mutator phenotype...
Treatment of confluence-arrested CHO-D422 cells for 48 h with low concentrations (0.5-3 nM) of the radiomimetic antibiotic neocarzinostatin resulted in an increase in up to 11-fold in the frequency of mutations at the hemizygous APRT locus. Analysis by PCR and DNA sequencing revealed that the mutations were a mixture of base substitutions, small deletions, and large-scale rearrangements. Base substitutions...
A chemical model system for cytochrome P450, a porphyrin and an oxidant, was used in Ames assay as a substitute for S9 mix. In the presence of tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride [Fe(F 5 P)Cl] and tert-butyl hydroperoxide (t-BuOOH), mutagenicity of N-nitrosodibutylamine (NDB) in Salmonella typhimurium TA1535 was detected. The mutagenicity depended on the pre-incubation...
To evaluate the eventual genetic damage induced by therapeutic exposure to 131 I, we have studied the presence of micronuclei (MN) in binucleated peripheral blood lymphocytes from a group of 28 hyperthyroidism patients who received 131 I sodium iodide, via oral administration. The study was conducted over time and blood samples were obtained before the treatment,...
We have investigated and compared DNA damage and cell killing induced in human and equine lymphocytes after in vitro X-irradiation. Our data show that the cytogenetic and the lethality effects are both greater in equine lymphocytes, but that the difference is wider for lethality. The ratios between doses inducing the same effect are 1.3, 1.7 and 9.4 for the number of binucleated cells with micronuclei,...
We examined the mutagenicity of cigarette smoker's urine in 32 healthy male cigarette smoker and 37 healthy male non-smoker. Twenty-four-hour urine specimens were subjected to blue rayon extraction which selectively adsorb polycyclic compounds, after which the elutions were fractionated by carboxymethyl cellulose column chromatography for removing antimutagenic compounds. The mutagens were measured...
Induction of polyploidy by vitamin B 2 (VB 2 ) was investigated in cultured Chinese hamster lung (CHL/IU) cells. We report that VB 2 in the form of needle crystals induces polyploidy via the formation of CHL/IU cells with more than one nucleus. The incidence of polyploid cells depended on the amount of needle crystals. No induction of polyploidy was observed when VB ...
Abnormalities in the p53 gene play an important role in genomic instability and tumorigenesis. Our previous work showed that p53 status is correlated with differential mutability in two closely related human lymphoblastoid cell lines, TK6 and WTK1. WTK1 cells, which contain a mutation in p53 (p53Ile 237 ) show a remarkably increased mutability, larger genetic alterations at the...
O 6 -Methylguanine (O 6 MeG) is important in induction of chromosome aberrations (abs), with the unusual property that new abs are produced in the second cycle after treatment; cells lacking repair by O 6 -alkylguanine DNA-alkyltransferase (AGT) have more abs at the second division (M2) than at the first (M1). These second-cycle abs are likely caused by attempted correction...
Neurofibromatosis type 1 (NF1) is among the most common human genetic disorders, having a constellation of cutaneous and skeletal manifestations, intellectual impairment, and an increased risk for a variety of malignancies. The NF1 gene has a high spontaneous mutation rate and is also associated with a variety of sporadic cancers in the general population. While a number of laboratories are involved...
Frequencies of spontaneously occurring and X-ray induced, stable and unstable types of chromosome aberrations in peripheral blood lymphocytes from two groups of radiosensitive patients, i.e., aplastic anemia (AA) and Diamond-Blackfan anemia (DBA), were determined. Two types of staining methods, i.e., chromosome painting with two cocktails of chromosome-specific DNA libraries (Nos. 1, 3, X and Nos...
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