Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage. 11 70

Rats treated with di(2-chloroethyl)methylamine (HN2), N-methyl-N-nitrosourea (MNUA) and N-ethyl-N-nitrosourea (ENUA) excrete significantly larger amounts of deoxycytidine (dC) and thymidine in their urine 0-24 h after treatment. Ethyl methanesulphonate (EMS) and dimethylnitrosamine (DMN) gave negative results in this respect but all five alkylating agents increased the excretion of 1-methyl-nicotinamide (1-meNmd). In addition, a larger quantity of 7-methylguanine (7MG) and uric acid was excreted after DMN treatment. 1,4-Dimethanesulphonoxybutane (myleran), 2,2-dichlorovinyl dimethyl phosphate (dichlorvos), 5-fluorouracil (5FU), cytosine arabinoside (araC), 2-acetylaminofluorene (AAF) and 7-bromomethylbenz-[a]anthracene (7-BrMBA) gave negative results.
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PMID:Increased urinary excretion of nucleic acid and nicotinamide derivatives by rats after treatment with alkylating agents. 12 32

The interaction of bacteriophage R17 with 8 compounds has been studied, comparing the contribution of degradation of ribonucleic acid to the total toxicity. Breaks in the RNA chain result from the hydrolysis of phosphotriesters and thus are a measure of the extent of O-alkylation and of the SN1-type mechanism of the reaction. With many alkylating agents mutagenicity and carcinogenicity increase with increasing SN1 character of the reaction. In experiments with methyl methanesulphonate no evidence of degradation was observed at up to 19 times the mean lethal dose (620 methylations/RNA molecule). Breaks in the RNA chain accounted for 1 in 10 of the lethal lesions with beta-hydroxyethyl methanesulphonate, 1 in 60 with bis-(2-chloromethyl)methylamine (nitrogen mustard, HN2), less than 1 in 125 with 2,2-dichlorvinyl dimethyl phosphate (dichlorovos, DDVP), and 1 in 200 with propylene oxide. The hydrolysis rate of bis-(2 chloroethyl)ether was too slow for any reaction to be detected. In reactions with the carcinogen bis-(2-chloromethyl)ether the toxicity observed could be accounted for by the formaldehyde produced on hydrolysis. Cross-linking of the bacteriophage components by formaldehyde reduced the survival range over which the physical state of the RNA could be studied. No evidence of RNA degradation was observed. Reaction of the formaldehyde led to a progressive loss of biological activity over 24 h, a loss which was partially reversed by dialysis.
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PMID:Assays for phosphotriester formation in the reaction of bacteriophage R17 with a group of alkylating agents. 17 45

Human and animal blood plasm precallikrein was studied as activated by the high-dispersed preparations of silica (aerosils) which carry on their surface various chemically grafted organic radicals. It is shown that hydrophilic silica containing -COOH, -HN2, -OH groups, contrary to the hydrophobic ones, are efficient in activating human plasm precallikrein. Precallikrein activation is dependent on concentration of hydrophilic aerosil, temperature and specific surface of the activator.
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PMID:[Plasma prekallikrein activation by highly dispersed organic silica]. 18 20

Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41 (Baker and Carpenter 1972). Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102 , two to mus(1)103, and one each to mus(1)104, mus(1)105 , and mus(1)106). Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair ( Boyd and Setlow 1976). Only the mei-41 mutants are hypersensitive to UV radiation, although several of the mutants exhibit sensitivity to gamma-rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9.
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PMID:Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. 18 27

The gut microcolony assay has been used to measure damage to intestinal crypts by single and split doses of 3 alkylating agents: mechlorethamine hydrochloride (HN2), bis-chloroethyl-nitrosourea (BCNU) and isopropyl methane sulphonate (IMS). The single-dose survival curves for whole crypts were distinguished by extrapolation numbers (3.0, 176 and 1.5 respectively) that were lower than most previously published values for assay by irradiation. Significant sparing of crypts occurred when doses of HN2 or BCNU, but not IMS, were given in 2 equal fractions separated by more than 2 h. Deduced D0 values for those cells from which crypts regenerate were 1.9 mg/kg HN2, 19 mg/kg BCNU and 487 mg/kg IMS.
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PMID:Ablation of murine jejunal crypts by alkylating agents. 21 78

The radioprotective drug, WR-2721 (S,2-[3-aminopropylamino]ethyl-phosphorothioic acid), has been studied in terms of its ability to (a) protect mice against mechlorethamine (HN2)-induced hematopoietic death, and (b) alter the ability of HN2 injections to induce growth delay in a solid tumor, the Line 1 lung carcinoma. When WR-2721 was injected ip 15 minutes before iv injections of HN2, it increased resistance to hematopoietic death by a factor of 2, and the protection declined with a half-life of 1.5-2.0 hours. Similar administration of both drugs failed to alter the responsiveness of the Line 1 lung carcinoma to HN2-induced growth delays, except when the HN2 was given within 15 minutes after WR-2721. This interaction of the two drugs, when given within 5-15 minutes of each other, does not appear to be true protection at the tumor site, but rather appears to result from HN2 inactivation in the blood. When HN2 is given 30-60 minutes after WR-2721, it is possible to obtain a twofold increase in the tumor delay without risking increased hematopoietic injury.
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PMID:Differential protection of normal and malignant tissues against the cytotoxic effects of mechlorethamine. 22 59

In this study 12 patients with mycosis fungoides were treated with whole body topical application of HN2. In addition 4 of these patients had gauzes moistened with the same HN2 solution placed upon plaques and tumours. 4 patients developed in allergic contact dermatitis, and this complication was overcome by percutaneous desensitizing in 3 of them. After starting hydration of plaques and tumours with HN2, the average time to obtain complete clinical remission was shorted from 4.4 to 2.5 months. A little later at the optimal histologic response, there was no or almost no cellular infiltration in 5 cases, while in 6 cases there was only a slight, unspecific, lymphocytic infiltrate in the dermis.
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PMID:Remissions of mycosis fungoides induced by nitrogen mustard (HN2). Topical treatment and hydration of tumours and plaques with HN2. Topical desensitization to HN2. A clinical and histopathological controlled study. 34 93

The effects of chemotherapeutica: 6 mercaptopurine (6 MP), nitrogen mustard (HN2) and cyclophosphamide (Cy) on T and B cells were studied in standardized experimental systems. From the histological and immunological results it was concluded that: (a) A course of 9 daily 6 MP injections affected antibody production only when given after antigenic stimulation. Histologically figures of mitotic death were found among proliferating cells of plasmacellular-germinal centre-and specific cellular reactions. It was concluded that a net mitotic death of 50% would account for the observed immunological and histological effects; (b) HN2 and Cy affected antibody production itself when administered during a very restricted period (1 through 3 days after ag.). Histologically only morphological changes were found in differentiating immature plasmacells and interphase death of cells involved in germinal centre reactions. Loss of responsiveness depended on the degree of interphase death of follicular elements. Cy interfered with the formation of T helper cells in thymus-dependent antibody production; (c) L-Asparaginase (1,000 U) only prevented the origination of T-helper cells. Neither antibody-producing cells nor their precursors were affected.
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PMID:Effects of drugs on immune responsiveness in rabbits. 34 95

Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant mutant types and to some actual problems of induced mutagenesis.
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PMID:Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis. 36 69


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