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1.
An arginine derivative, benzoyl-L-arginineamide, when nitrosated, showed a powerful mutagenic action on and . The active principle was identified to be 4-benzoylamido-4-carboxamidon(N-nitroso)butylcyanamide. The mutagenic activity of the new compound was more than 30 times higher than that of N-methyl-N′-nitro-N-nitrosoguanidine at neutral pH. 相似文献
2.
Elena C. McCoy G.David McCoy Herbert S. Rosenkranz 《Biochemical and biophysical research communications》1982,108(3):1362-1367
Characterization of a mutant strain (TA98/1,8-DNP6) resistant to the mutagenicity of nitrated polycyclic aromatic hydrocarbons (nitroarenes) revealed that it was also non-responsive to the mutagenic action of nitroso- and N-hydroxylaminoarenes. The mutant strain was fully sensitive to the mutagenic action of the corresponding hydroxamic acid ester. These results suggest that TA98/1,8-DNP6 is deficient in a specific esterifying enzyme and that esterification of the penultimate mutagenic metabolites of nitro- and aminoarenes (, arylhydroxylamines) to form potent electrophiles is controlled by a specific gene. 相似文献
3.
P.G. Wislocki A.W. Wood R.L. Chang W. Levin H. Yagi O. Hernandez D.M. Jerina A.H. Conney 《Biochemical and biophysical research communications》1976,68(3):1006-1012
(±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BP 7,8-diol-9,10-epoxide) is a suspected metabolite of benzo[a]pyrene that is highly mutagenic and toxic in several strains of and in cultured Chinese hamster V79 cells. BP 7,8-diol-9,10-epoxide was approximately 5, 10 and 40 times more mutagenic than benzo[a]pyrene 4,5-oxide (BP 4,5-oxide) in strains TA 98 and TA 100 of and in V79 cells, respectively. Both compounds were equally mutagenic to strain TA 1538 and non-mutagenic to strain TA 1535 of . The diol epoxide was toxic to the four bacterial strains at 0.5–2.0 nmole/plate, whereas BP 4,5-oxide was nontoxic at these concentrations. In V79 cells, the diol epoxide was about 60-fold more cytotoxic than BP 4,5-oxide. 相似文献
4.
C Malaveille H Bartsch B Tierney P L Grover P Sims 《Biochemical and biophysical research communications》1978,83(4):1468-1473
7,12-Dimethylbenz[a]anthracene and its 3,4-, 5,6-, 8,9- and 10,11-dihydrodiols have been tested for mutagenicity towards . TA100 in the presence of rat-liver post-mitochondrial supernatants from Aroclor-treated rats. At non-toxic concentrations, the non-K-region 3,4-dihydrodiol was six-fold more active than the parent hydrocarbon. At these concentrations, the 8,9-dihydrodiol showed some mutagenic activity, but the 5,6- and 10,11-dihydrodiols were inactive. 相似文献
5.
The activation pathway of 2-acetylaminofluorene (AAF) to N-hydroxy-2-amino-fluorene (N-OH-AF), a potent mutagen to , by guinea pig liver postmitochondrial supernatant fraction (S-9 fraction) was studied. 2-Aminofluorene (AF), as well as N-hydroxy-2-acetylaminofluorene (N-OH-AAF, Takeishi et al., Mutation Res. in press), was detected as a metabolite of AAF. The mutagenicities of AF and N-OH-AAF comparable to that of AAF were inhibited by antiserum against NADPH-cytochrome reductase and by paraoxon, respectively. These data indicate that in the mutagenic activation of AAF, N-OH-AF can be produced by both N-hydroxylation of AF and deacetylation of N-OH-AAF. Furthermore, the data on the relative contribution of paraoxon-sensitive activation pathway to mutagenicities of AAF and N-OH-AAF led to a conclusion that deacetylation of AAF followed by N-hydroxylation to produce N-OH-AF is the main pathway for the mutagenic activation of AAF by guinea pig liver S-9 fraction. 相似文献
6.
B R Brown W J Firth L W Yielding 《Biochemical and biophysical research communications》1979,86(4):1139-1145
The frameshift mutagenic mechanism for acridines has been attributed to the intercalative type of association between acridines and nucleic acids. However, it appears that these molecular details are insufficient to explain the frameshifting process. In order to design an effective drug probe to analyze the interactions of acridines leading to frameshifting, an azide analog of 9-aminoacridine was studied in Ames' strains. The surprising findings were that by substituting an amino group at the 9 ring position with an azido group, the mutagenicity was converted from frameshifter to base-pair substitution. 相似文献
7.
A spectrofluorimetric investigation of calf thymus DNA modified by BP diolepoxide and 1-pyrenyloxirane 总被引:1,自引:0,他引:1
N C Yang L K Ng S B Neoh D Leonov 《Biochemical and biophysical research communications》1978,82(3):929-934
7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BP diolepoxide, ) and 1-pyrenyloxirane () bind chemically to calf thymus DNA. The fluorescence efficiency of pyrenyl groups in mutagen modified DNA varies appreciably with its conformation and decreases in the order: pyrenees, modified denatured DNA and modified native DNA. A particularly interesting observation is that the fluorescence efficiency of mutagen modified DNA intensifies substantially upon denaturation. Our results suggest that the pyrenyl groups in mutagen modified DNA are intercalated between the base pairs of DNA. Since both and are powerful frame-shifting mutagens for S. typhimurium TA-98, the intercalative covalent binding of these compounds to DNA may provide a molecular basis for their mutagenic activity. 相似文献
8.
The ability of L-cysteine to inhibit azide-metabolite synthesis and mutagenecity is investigated in Salmonella typhimurium TA1530 and cys E6 strains. L-cysteine specifically inhibits the synthesis of the mutagenic azide metabolite as other compounds containing SH group did not affect the production of this metabolite. Azide mutagenicity is completely inhibited by L-cysteine at a concentration (5 μmoles/plate) where the metabolite mutagenicity was not affected. can reverse the L-cysteine mediated inhibition of the metabolite synthesis and thus mutagenicity in the same strains. These results suggest that may be required to synthesize the azide metabolite or its precursor. 相似文献
9.
Lack of mutagenicity and metabolic inactivation of aphidicolin by rat liver microsomes 总被引:1,自引:0,他引:1
G Pedrali-Noy G Mazza F Focher S Spadari 《Biochemical and biophysical research communications》1980,93(4):1094-1103
In view of the possible utilization of aphidicolin, a specific inhibitor of DNA polymerase α, in the treatment of neoplastic diseases, it seemed important to assess the mutagenic effect of the drug and the possible modification induced by metabolic activation in the liver. This paper shows that aphidicolin lacks mutagenicity in the Ames' -microsome test in agreement with our previous observation that it does not induce DNA repair synthesis in HeLa cells. During the studies of mutagenicity we have observed that aphidicolin is converted to inactive derivative(s) by rat liver microsomal oxidases. The reaction is dependent on time and temperature and requires NADP+ and glucose-6-P. The metabolites are not mutagenic and they do not induce DNA repair synthesis in HeLa cells. Therefore the possible anti-cancer use of aphidicolin is not hampered by its partial metabolic inactivation in liver. Our results suggest however that aphidicolin will possibly be clinically useful at concentrations higher than those expected from our studies with human DNA polymerase and human neoplastic cell lines . The metabolic derivative(s) of aphidicolin is inactive both against cellular DNA polymerase α and Herpes simplex viral DNA polymerase. 相似文献
10.
C de Meester F Poncelet M Roberfroid M Mercier 《Biochemical and biophysical research communications》1978,80(2):298-305
Incubation of strains TA1530 and TA1535 in the presence of gaseous butadiene increased the number of his+ revertants/plate. This mutagenic effect occured in absence of fortified S-9 rat liver fraction. In its presence, the mutagenic effect seemed to be dependent on its composition. With butadiene monoxide, a reversion to histidine prototrophy was obtained without metabolic activation with strains TA1530, TA1535 and TA100. Butadiene monoxide might be a possible primary metabolite of butadiene. 相似文献
11.
B F Coles J R Smith R C Garner 《Biochemical and biophysical research communications》1977,76(3):888-892
Racemic 3a,8a-dihydrofuro[2,3-b]benzofuran has been chemically synthesized as a model of the vinyl ether structure of aflatoxin B1 (AFB1) and tested for mutagenicity. In the presence of 9000g rat liver supernatant fraction the compound induced his+ revertant colonies in TA 100 but with only one five-thousandth the activity of AFB1. No mutagenicity was found when strain TA98 was used. Omission of the rat liver preparation abolished mutagenic activity. The reduced compound, tetrahydrofurobenzofuran, was inactive as a mutagen either in the presence or absence of the rat liver supernatant. 相似文献
12.
Infidelity of DNA synthesis by reverse transcriptase 总被引:3,自引:0,他引:3
C F Springgate N Battula L A Loeb 《Biochemical and biophysical research communications》1973,52(2):401-406
The fidelity of purified DNA polymerase from avian myeloblastosis virus in precisely copying polynucleotide templates was determined. With poly (dA-dT) · poly (dA-dT) as a template, one molecule of the incorrect basepaired nucleotide (dCTP) is incorporated for every 6000 nucleotides polymerized. When copying the ribo strand of poly (rA) · poly (dT) the error rate is approximately one in 600. It is suggested that the enzyme makes similar errors and thus could be mutagenic. 相似文献
13.
Cornelia Harte 《Mutation research》1975,30(1):71-75
Pollen of Antirrhinum majus was irradiated with radiowaves (γ = 1.5 m; field strength 1.5 V/m) in 3 series for 4, 12 and 43 h, then crossed on styles of emasculated untreated flowers. After selfing of the M1 generation an increase in embryonic lethality and in mutations for characters of the seedlings and young plants was observed. These observations confirmed the mutagenic action of the treatment that was described earlier in Vicia faba and Oenothera hookeri. 相似文献
14.
The effect of Mn2+, a known mutagen, on the fidelity of DNA synthesis by avian myeloblastosis DNA polymerase has been determined. Substitution of Mn2+ for Mg2+ leads to an enhanced incorporation of noncomplementary deoxynucleotides as well as complementary ribonucleotides with either poly (A) or poly (C) as templates. Since this polymerase lacks any detectable deoxyribonuclease activity, the mutagenic effect of Mn2+ in promoting errors in base-pairing does not result from any diminished proof-reading function. 相似文献
15.
The mutagenic activity toward TA 98 and TA 100 was investigated by heat treatment at temperatures up to 200°C of meat with identified components such as protein, adenine, creatine and a mixture of each of the 17 amino acids or glucose. Mutagenicity of these nitrogenous compounds was detected at the temperature of 150°C by adding glucose, consequently the yield of mutagenic activity by heating creatine and glucose was remarkably high. It is assumed that mutagens would be formed by the reaction of creatine and sugars during cooking of meat. 相似文献
16.
A W Wood W Levin D Ryan P E Thomas H Yagi H D Mah D R Thakker D M Jerina A H Conney 《Biochemical and biophysical research communications》1977,78(3):847-854
Chrysene and the 3 metabolically possible vicinal dihydrodiols of chrysene were tested for mutagenicity towards strain TA100 in the presence of hepatic microsomes or a highly purified hepatic microsomal monooxygenase system. The products formed during the metabolic activation of chrysene 1,2-dihydrodiol were more than 20 times as mutagenic to the bacteria than the metabolites formed from chrysene, chrysene 3,4-dihydrodiol or chrysene 5,6-dihydrodiol. When the double bond in the 3,4-position of chrysene 1,2-dihydrodiol was saturated, the resulting tetrahydrodiol could not be metabolically activated. These results, which strongly suggest that chrysene 1,2-dihydrodiol is activated by metabolism to either or both of the diastereomeric chrysene 1,2-diol-3,4-epoxides, provide additional support for the bay region theory of polycyclic hydrocarbon carcinogenicity. 相似文献
17.
L W Yielding T L Riley K L Yielding 《Biochemical and biophysical research communications》1976,68(4):1356-1361
Caffeine and chloroquine were administered to pregnant mice at doses which were non-teratogenic. Nevertheless, these dose levels enhanced significantly the number of cleft palates produced by 200 rads x-ray. The combination of chloroquine with 200 rads x-ray also resulted in a substantially higher incidence of tail abnormalities. Although the mechanisms of action for most teratogens are undefined, mutagenic damage to DNA has been implicated. We propose a “co-teratogenic” mechanism by which non-teratogenic agents enhance the effectiveness of gene damage in producing fetal abnormalties. 相似文献
18.
Inactivation of Q beta RNA by electrophiles 总被引:1,自引:0,他引:1
A Kondorosi I Fedorcsák F Solymosy L Ehrenberg S Osterman-Golkar 《Mutation research》1973,17(2):149-161
Methyl, ethyl and isopropyl methanesulfonates (MMS, EMS, iPMS), diethyl pyrocarbonate (DEP) and autoclaved irradiated sucrose and glucose (active principles presumably α,β-unsaturated carbonyl compounds) inactivated the transfectivity of β RNA in one-hit processes. In the case of DEP, nealy every carbethoxy group introduced inactivated, whereas several alkyls from the methanesulfonates per RNA molecule seemed te be tolerated. 1,2-Dibromoethane was a relatively strong inhibitor of RNA transfectivity in the presence of thioglycol, probably via the formation of a more reactive “half mustard”.Compared with isolated RNA, the complete β phage was somewhat protected against methanesulfonates but slightly more sensitive to the irradiated sugars and distinctly more sensitive to DEP, indicating that the two latter compounds may inactivate in reactions with coat proteins.The negative tests with the strongly mutagenic 2,3,7,8-tetrachlorodibenzdioxin suggest that intercalating agents are probably not active towards RNA.The decrease of the trasnfectivity of β RNA may be used as a sensitive system to determine reactivity towards nucleic acids of environmental pollutants. 相似文献
19.
20.
M Maeda H Kobayashi M Futai Y Anraku 《Biochemical and biophysical research communications》1976,70(1):228-234
The term, xeroderma pigmentosum variants designates patients who suffer from the clinical manifestations of the disease, but whose cells have normal rates of excision repair of UV-induced lesions in DNA. In contrast to normal human fibroblasts, if cells from such variants are maintained in medium containing caffeine from immediately following exposure to UV until the survivors have undergone three doublings, the cytotoxic and mutagenic effect of UV light is dramatically increased. In the presence of 0.7mM caffeine, the slope of the UV survival curve increases 3-fold. Similarly, the slope of the curve describing the frequency of mutations to azaguanine resistance induced by UV as a function of dose is 3-fold steeper. 相似文献