共查询到20条相似文献,搜索用时 31 毫秒
1.
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
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.
The active principle responsible for the mutagenicity of methylguanidine nitrosated in weakly acidic conditions and in simulated gastric juice was identified to be methylnitrosocyanamide. This compound was quite similar to N-methyl-N'-nitro-N-nitrosoguanidine in their mutagenic quality, while its mutagenic activity was about 16 times higher for a strain of than that of the latter at neutral pH. 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.
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
6.
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
7.
N(4)-amino-and N(4)-hydroxycytosines as base analogue mutagens 总被引:2,自引:0,他引:2
N(4)-Aminocytosine [N(4)NH2C] and N(4)-amino-2′-deoxycytidine [N(4)NH2dC] are highly mutagenic for Escherichia coli and phage φ 80 but not for T4. There is some evidence that they are incorporated into the φ 80 DNA but could not be detected in the bacterial DNA.N(4)-Hydroxy-5,6-dihydro-6-hydroxylaminodeoxycytidine (di-NHOH-dC) is mutagenic for φ 80 and E. coli, but N(4)-hydroxydeoxycytidine [N(4)OH-dC] only has a strong inactivating effect. 相似文献
8.
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
9.
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
10.
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
11.
12.
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
13.
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
14.
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
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.
Theodore Dashman 《Life sciences》1980,27(15):1415-1422
The enol-ether amino acid, L-2-amino-4-methoxy--butenoic acid (AMTB) is an inhibitor of porphobilinogen synthase (PBG synthase) when added prior to the addition of the substrate δ-aminolevulinic acid. The inhibition of PBG synthase by several stereoisomers and analogues of AMTB was investigated to determine those structural features of AMTB which may be necessary for inhibition. The D- isomer was also an inhibitor after preincubation, whereas the L- isomer inhibited with or without preincubation. The amino acid analogues, DL-vinylglycine, DL-2-aminobutanoic acid, the reduced form of L-2-amino-4-methoxy--3-butenoic acid, L-2-amino-4-(2-aminoethoxy)--3-butenoic acid and its reduced congener did not inhibit PBG synthase even with preincubation. This structure activity relationship indicates that the double bond and methoxy moiety of L-2-amino-4-methoxy--3-butenoic acid are probably required for inhibition.Heme, when preincubated with PBG synthase, was an inactivator of the enzyme. However, when both L-2-amino-4-methoxy--3-butenoic acid and heme were simulatneously preincubated with PBG synthase, inactivation of the enzyme was greater than with either compound separately. The possibility of multiple catalytic sites was suggested by the use of multiple inhibition kinetics in the presence of heme and L-2-amino-4-methoxy--3-butenoic acid. 相似文献
17.
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
18.
4β,5-Epoxy-5β-androstane-3,17-dione (), 17β-hydroxy-4β,5-epoxy-5β-androstan-3-one () and 17β-acetoxy-4β,5-epoxy-5β-androstan-3-one () were treated with anhydrous hydrogen fluoride in pyridine (70% solution) at 55° and yielded the corresponding 4-en-4-ols e.g. 4-hydroxy-4-androstene-3, 17-dione ().As the reaction temperature was lowered each epoxide formed a second product which, at ?75°, was the major component of the reaction mixture and was identified as the 5α-fluoro-4α-ol derivative of the parent enone, e.g. 4α-hydroxy-5-fluoro-5α-androstane-3,17-dione (). These fluorohydrins are thermally unstable, losing hydrogen fluoride.The acetates of the fluorohydrins were also prepared, characterized, and shown to be more stable than the parent alcohols. 相似文献
19.
A series of analogues of dopamine (DA) with varying degrees of conformational flexibility have been examined as potential substrates or competitive inhibitors of the enzyme norepinephrine N-methyltransferase (NMT). A conformationally defined (rigid) analogue of the fully extended conformation of DA, 2-amino-6, 7-dihydroxybenzonorbornene hydrobromide (; 6, 7-D2HX) proved to be a better substrate than the non-catechol parent 2-aminobenzonorbornene (; 2HX). However, analogues and displayed equivalent competitive inhibitory activity toward phenylethanolamine (PEA). Neither 6, 7-ADTN (5), a DA analogue in the 2-aminotetralin (2AT) system, nor 6, 7-DTHIQ (), a DA analogue in the tetrahydroisoquinoline (THIQ) system, showed substrate activity; 6, 7-ADTN was a poorer competitive inhibitor than the parent 2AT but 6, 7-DTHIQ was a better competitive inhibitor than its parent, THIQ (). A tricyclic conformationally defined analogue of 6, 7-ADTN was devoid of either substrate or inhibitory activity. From these results it may be concluded that a fully extended side chain conformation is required for NMT substrate activity, and the better substrate activity for 6, 7-D2HX compared to is consistent with a proper catechol orientation for interaction with the norepinephrine (NE) binding site of NMT. 相似文献
20.
R B Frydman J Awruch M L Tomaro B Frydman 《Biochemical and biophysical research communications》1979,87(3):928-935
Hemin XIII , hemin III , and iron were enzymatically oxidized by a microsomal heme oxygenase preparation from rat liver. These are all better substrates of the oxygenase than the natural substrate, hemin IX . The enzymatic oxidation was selective for the α-methine bridge and in every case only the α-biliverdins were obtained. The latter were readily reduced by biliverdin reductase to the corresponding α-bilirubins. The absence of isomers in addition to the α-bilirubins was established by preparing the derived azopigments and by using [α-14C] and [α-14C] as substrates. The chemical oxidation of , , and gave the expected mixture of biliverdins. It is concluded that heme oxygenase is not specific for hemin IX. On the other hand, the enzyme is highly selective for the α-methine bridge, defined as the methine opposed to that flanked by the 6,7-propionic acid residues. 相似文献