Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00249 (Mutagen)
 5,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drosophila melanogaster males from a Basc stock were mutagenized with either X-rays, ethyl methanesulfonate (EMS), or nitrogen mustard (HN2). Groups of identically treated males were crossed to different types of female. Sex-linked recessive lethals were scored as a genetic end point. The females used were homozygous for X-chromosomal mutations (mus(1)101D1, mus(1)104D1, mei-9 or mei-41D5) which lead to defective DNA repair and which increase the mutagen sensitivity of larvae. Females from a white stock with normal DNA repair capacities served as controls. The premutational lesions induced in mature sperm are only processed after insemination by the maternal enzyme systems present in the oocytes. Differences in the efficiency of the processing of lesions can lead to maternal effects on the frequency of mutations recovered from mutagenized sperm. It was found that, with the exception of mus(1)104D1, all mutants analysed significantly modify the mutation fixation of one or more types of premutational lesions. The most drastic effect is found with the mus(1)101D1 stock in which HN2-induced DNA cross-links do not lead to sex-linked recessive lethals. It is assumed that mus(1)101D1 is defective in an early step of DNA cross-link repair. Our first set of data clearly demonstrates that the study of maternal effects in Drosophila is an efficient tool to analyse the in vivo function of repair mutations on chemically induced mutagenesis.
 ...
PMID:Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage. 11 70

Simple, rapid colorimetric tests for lysogenic induction (the derepression of a latent bacterial virus) are described. A quantitative test and a more rapid semiquantitative test are based on the assay of the beta-galactosidase synthesized from lacZ gene fused to an operon under lambda repressor control. These biochemical "inductests" are suitable for screening programs designed to detect agents that damage DNA and that are of potential interest in carcinogenesis and cancer chemotherapy.
Environ Mutagen 1979
PMID:A colorimetric assay of lysogenic induction designed for screening potential carcinogenic and carcinostatic agents. 16 85

The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays.
 ...
PMID:Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP. 19 23

The substrate specificity of the uvr endonuclease, the product of the uvrA, uvrB, and uvrC genes is reviewed. It is suggested that the relatively well-defined substrate specificity of this repair enzyme is useful as a guide in determining the nature of the DNA-lesion caused by a given mutagen.
Environ Mutagen 1979
PMID:Substrate-specificity of uvr excision repair. 23 62

The furocoumarin psoralen can form both monoadducts and cross-links with DNA when combined with 360-nm radiation, whereas the analog angelicin can form monoadducts only. Psoralen plus 360-nm radiation causes mutation induction with a slope of 2 (log-log plot) for a radiation-insensitive strain, whereas angelicin action with 360-nm radiation displays a slope of unity. For a radiation-sensitive mutant defective in the excision-repair pathway, the actions of both angelicin and psoralen plus 360-nm radiation exhibit one-target kinetics, but at higher exposures psoralen plus 360-nm radiation assumes a slope of 2. The excision-repair-defective strain is considerably more sensitive to the furocoumarins plus 360-nm radiation than is the radiation-insensitive strain, both for killing and mutation induction. The simplest explanation for the data is that both cross-links and monoadducts, formed by furocoumarins with DNA when exposed to 360-nm radiation, are capable of inducing mutations, and that monoadducts are repaired 20 times more efficiently than cross-links by the excision-repair pathway.
Environ Mutagen 1979
PMID:Mutagenicity of cross-links and monoadducts of furocoumarins (psoralen and angelicin) induced by 360-nm radiation in excision-repair-defective and radiation-insensitive strains of Saccharomyces cerevisiae. 39 5

Phototherapy has been shown to be an effective therapy for severe neonatal jaundice. However, because of its seemingly innocuous effect on normal babies, this therapeutic modality has been widely used to prevent jaundice in circumstances where it may be neither necessary nor beneficial. The present report summarizes results which indicate that phototherapy is endowed with DNA-modifying properties and has therefore the potential for inducing genetic and carcinogenic effects. These disconcerting findings concerning the long-term hazardous consequences of an accepted therapeutic procedure require that the unique physiologic and pharmacologic characteristics of the newborn populations be recognized when assessing the risks and benefits of phototherapy.
Environ Mutagen 1979
PMID:Phototherapy for neonatal hyperbilirubinemia--a potential environmental health hazard to newborn infants: a review. 39 16

Induction of 8-azaguanine-resistant mutation, DNA single-strand breaks, and chromosome aberrations by treatment with ethyl methanesulfonate (EMS), N-methyl-N'nitro-N-nitrosoguanidine (MNNG), nitrogen mustard hydrochloride (HN2), or 4-nitroquinoline 1-oxide (4-NQO) was compared under similar experimental conditions using cultured FM3A cells from a C3H mouse mammary carcinoma. All the chemicals induced 8-azaguanine-resistant mutations and chromosome aberrations in a dose-dependent manner; a good correlation between the two activities was demonstrated. An alkaline sucrose gradient method demonstrated that DNA single-strand breaks were induced only in a high dose range by 1- and 24-hr treatment with the chemicals. One exception was that a 1-hr treatment with HN2 produced an anomalous sedimentation pattern. These data suggest that caution is necessary for the interpretation of results obtained by the alkaline sucrose gradient analysis, and that examination of mutagenicity and chromosome aberrations is more feasible as screening procedures for potential mutagens than analysis of DNA single-strand breaks.
 ...
PMID:Comparison of mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations in cultured mouse cells by potent mutagens. 41 23

The separate in vitro effects of HN2 and L-PAM on resting and stimulated peripheral blood lymphocytes were evaluated with biochemical and morphologic experimental endpoints. Both alkylating agents caused dose-dependent reduction of protein, RNA, and DNA synthesis, but the patterns of diminution differed. The number of cells staining with Erythrosin B, as a toxicity indicator, also rose with higher drug concentrations, but a large proportion of lymphocytes remained unstained even at the maximum drug dose. Stimulation with PHA partially nullified the suppression caused by HN2 but did not influence the effects of L-PAM. Exposure to PWM rendered the in vitro HN2 innocuous but L-PAM remained cytotoxic. Simultaneous lectin-induced blastogenesis proceeded unaltered. Finally, comparisons between 72 and 4 hr drug exposures imply that interference with intracellular synthesis occurs promptly, continues after drug removal, and is related quantitatively to drug concentration rather than to duration of contact.
 ...
PMID:In vitro effects of single alkylating agents on normal peripheral blood lymphocytes. 46 67

CHO cells were synchronized in G1 phase and treated with MMS or HN2. The subsequent rate of DNA replication was found to be reduced in a dose-dependent manner. In addition, 2 X 10(-3 M and 3 X 10(-3) M MMS resulted in a 3--4 h delay prior to the initiation of S phase. If the cells were held for 8 h in hydroxyurea after MMS treatment, no subsequent lag in DNA synthesis was seen after removal of the hydroxyurea. The entry of confluent cells into S phase was found to be delayed 7 h upon trypsinizing and replating. Treatment of these cells with MMS resulted in a reduced rate of DNA replication, but no further delay in its initiation. Repair replication was found to continue at a constant rate for at least 12 h following MMS treatment of cells under all of these conditions. At the concentrations used in these experiments MMS severely inhibited the rate of protein synthesis, but HN2 had little effect. By comparing both the kinetics of repair replication and recovery of protein synthesis with the rate of DNA replication, it was concluded that the initial, severe reduction in rate following MMS treatment was probably due to an inhibition of protein synthesis.
 ...
PMID:The recovery of mammalian cells treated with methyl methanesulfonate, nitrogen mustard or UV light. I. The effect of alkylation products on DNA replication. 48 40

CHO cells were synchronized 2 G1 phase and treated with UV light or HN2. These treatments resulted in a dose-dependent reduction in the rate of DNA replication and cell survival. Holding UV-irradiated cells in G1 phase (in HU medium) for an additional 10 h prior to their release into S phase did not assist recovery as measured by either of these criteria. The survival of cells treated with HN2 was also not enhanced by this recovery period. However, following 2 X 10(-5) M HN2 the rate of DNA replication increased from 30% to 70% of the control level when the period in HU medium was extended to 14 h. The induction of cross-links following HN2 treatment of asynchronous cells was shown to be dose dependent. Subsequent incubation in fresh medium resulted in complete recovery within 20 h at concentrations of HN2 up to 10(-5) M, and at 2 X 10(-5) M HN2, 75% of the cross-links were removed at 14 h post treatment.
 ...
PMID:The recovery of mammalian cells treated with methyl methanesolfonate, nitrogen mustard or UV light. II. The importance of DNA repair prior to the initiation of S phase. 48 41


1 2 3 4 5 6 7 8 9 10 Next >>