共查询到20条相似文献,搜索用时 46 毫秒
1.
T J Slaga S Thompson D L Berry J Digiovanni M R Juchau A Viaje 《Chemico-biological interactions》1977,17(3):297-312
The effects of benzoflavones on skin tumor initiation by polycyclic hydrocarbons and epidermal aryl hydrocarbon hydroxylase were investigated. 7,8-Benzoflavone (7,8-BF) was found to be a potent inhibitor of the inhibition of skin tumors by 3-methylcholanthrene (MC) as well as 7,12-dimethylbenz(a)anthracene (DMBA). 5,6-Benzoflavone(5,6-BF) inhibited tumor initiation by MC and DMBA, but to a lesser degree than 7,8-BF. Dose-response studies of the capacity of 7,8-BF to inhibit DMBA tumor initiation revealed that 7,8-BF was an effective inhibitor at 2.5 microgram and a maximum inhibition of 90% occurred at 100 microgram of 7,8-FB. The tumor initiating ability of 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHMe-12MeBA) was not inhibited by 7,8-BF. Epidermal aryl hydrocarbon(benzo(a)pyrene hydroxylase(AHH) was increased by 5,6-BF and either had no effect or was slightly inhibited by 7,8-BF when given either topically or i.p. Both flavones when added directly to the assay tubes inhibited the in vitro epidermal AHH activity from control and MC pretreated mice by greater than 75%. When added in vitro, 7,8-BF and 5,6-BF inhibited epidermally mediated covalent binding of radioactive DMBA and dibenz(a,h)anthracene to DNA by 50% or more. The inhibition of skin tumor initiation by 7,8-BF and 5,6-BF appears to be partially related to its ability to inhibit the formation of electrophilic intermediates. 相似文献
2.
Mutagenicity of reactive derivatives of carcinogenic hydrocarbons: evidence of DNA repair 总被引:1,自引:0,他引:1
The ability of cellular DNA repair enzymes, which are active on ultraviolet light-induced lesions in DNA, to recognize and repair damage induced in DNA by exposure to carcinogenic polycylic hydrocarbons was investigated and the effect of such repair processes on the mutagenicity of the hydrocarbons determined. The carcinogenic hydrocarbos, 7-bromomethylbenz[a]anthracene (7-BrMeBA) and 7-bromomethyl-12-methylbenz[a]anthracene (7-BrMe-12-MeBA), chosen for this study because they form well characterized, stable products with DNA, were dissolved at various concentrations in acetone, added under mild conditions to biologically active DNA isolated from Bacillus subtilis, and the reaction stopped by ethanol precipitation. The hydrocarbons were determined by specific radioactivity to be covalently linked to DNA at a frequency of from 1–5 per 1000 nucleotides. An increased frequency of bound hydrocarbon molecules was directly correlated with a decrease in the buoyant density of the DNA as measured in analytical CsCl centrifugation studies. The samples of hydrocarbon-bound DNA were tested for survival of biological activity and for the frequency of induced forward mutations in two recipient strains (hcr+ and hcr?) of Bacillus subtilis which differ in their ability to repair ultraviolet light-induced lesions in DNA. The survival of the biological activity was significantly higher in the repairing strain (hcr+). A higher frequency of mutations was detected in the repairing strain as well. The loss of transforming activity and the increase in the frequency of mutations (up to 20-fold) was directly proportional to the amount of hydrocarbon bound to the DNA samples. The majority of these mutations proved unable to revert spontaneously. Finally, the ability of highly purified rat liver endonuclease, shown to recognize lesions in UV-irradiated DNA, to recognize such hydrocarbon lesions was investigated. Tritiated 7-BrMeBA-treated DNAs exposed to the enzyme were found to sustain single-strand nicks in proportion to the amount of hydrocarbon bound while untreated DNA remained substantially intact. The action of the endonuclease appeared to result in an increase in the biological activity of DNA containing hydrocarbon residues when this was assayed in the hcr? mutant. 相似文献
3.
James W. Flesher 《Life sciences》1981,28(10):1175-1181
Binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene to calf thymus DNA was negligible (1.2 μmole hydrocarbon/mole DNA-P) in the absence of microsomal enzymes whereas in the presence of liver microsomes from unpretreated rats or from rats pretreated with 3-methylcholanthrene binding was greatly enhanced (11.6 and 16.2 μmole hydrocarbon/mole DNA-P respectively). In contrast, the acetate ester of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene readily bound to DNA non-enzymatically (9.1 μmole hydrocarbon/mole DNA-P). In the presence of a 3′-phosphoadenosine-5′-phosphosulfate (PAPS) generating system, the binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene was independent of sulfate ion. ATP enhanced non-enzymatic binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene to DNA whereas CTP, β,γ-methylene-ATP, and ADP were much less effective suggesting a certain specificity for adenosine in addition to a high energy triphosphate for high binding. These observations suggest that 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene may be converted to a phosphate ester which, like 5-fluoro-7-acetoxymethyl-12-methylbenz(a)anthracene, readily binds to DNA. 相似文献
4.
W H Swallow K Pal D H Phillips P L Grover P Sims 《Chemico-biological interactions》1983,47(3):347-361
The metabolism of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and of 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA) into solvent- and water-soluble and protein-bound derivatives has been examined in rat liver and adrenal homogenates and in rat adrenocortical cells in culture. Although the overall extents of metabolism of the substrates by the two types of homogenate were similar, there was twice as much binding to protein in incubations with the 7-hydroxymethyl derivative. Rat adrenal cells in culture metabolized DMBA more extensively than 7-OHM-12-MBA and converted much more of the parent hydrocarbon into water-soluble derivatives. Both hydrocarbons were metabolized to yield dihydrodiols that were separated and identified by high performance liquid chromatography (HPLC). The 8,9-dihydrodiol was the major dihydrodiol formed from DMBA but, with 7-OHM-12-MBA as substrate, metabolism was diverted to the 10,11- and 3,4-positions in adrenal and hepatic preparations respectively. The viability of rat adrenocortical cells in culture, as measured by trypan blue exclusion, did not appear to be affected by treatment with DMBA, 7-OHM-12-MBA, the sulphate ester of 7-OHM-12-MBA or by 3,4-dihydro-3,4-dihydroxy-7-hydroxymethyl-12-methylbenz[a]anthracene. 相似文献
5.
The antimutagenic effect of selenium as sodium selenite, sodium selenate, selenium dioxide, and seleno-methionine was studied
in the AmesSalmonella/microsome mutagenicity test using 7,12-dimethylbenz(a)anthracene (DMBA) and some of its metabolites. Selenium (20 ppm) as
sodium selenite reduced the number of histidine revertants on plates containing up to 100 μg DMBA/plate. Increasing concentrations
of selenium as sodium selenite, sodium selenate, and selenium dioxide up to 40 ppm Se progressively decreased the number of
revertants caused by 50 μg DMBA. DMBA and its metabolites 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene,
and 3-hydroxy-7,12-dimethylbenz(a)anthracene were mutagenic forSalmonella typhimurium TA100 in the presence of an S-9 mixture. Selenium supplementation as Na2SeO3 reduced the number of revertants induced by these metabolites to background levels. The antimutagenic effect of inorganic
selenium compounds cannot be explained by toxicity of selenium as determined by viability tests withSalmonella typhimurium TA100. Selenium supplementation in all forms examined, except sodium selenate, decreased the rate of spontaneous reversion.
Selenium as sodium selenate was slightly mutagenic at concentrations of 4 ppm or less. Higher concentration of Na2SeO4 inhibited the mutagenicity of DMBA. The present studies support the anticarcinogenic potential of selenium and indicate that
form and concentration are important factors in this trace element's efficacy. 相似文献
6.
Peter P. Fu Ming W. Chou Shen K. Yang 《Biochemical and biophysical research communications》1982,106(3):940-946
While metabolism of benz[a]anthracene by rat liver microsomes produced a (+)5R,6R-dihydrodiol as the major enantiomer, metabolism of 12-methylbenz[a]anthracene under similar conditions gave a (?)5S,6S-dihydrodiol as the major enantiomer. This is the first example indicating that the methyl substituent of a polycyclic aromatic hydrocarbon can drastically alter the stereoselective preference of the microsomal drug-metabolizing enzyme systems toward a substrate molecule in the formation of a dihydrodiol metabolite at an unsubstituted aromatic double bond. 相似文献
7.
1,1,1-Trichloropropene 2,3-oxide (TCPO), a known inhibitor of the enzyme epoxide hydrase, inhibits binding of the carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), to the DNA of secondary mouse embryo cell cultures under conditions which do not appreciably decrease the overall metabolism of this carcinogen. This suggests that the formation of a transdihydrodiol is a necessary step in the metabolic pathway leading to DNA binding and that binding probably occurs through the generation of a reactive diol-epoxide. In concert with this, the major DMBA-DNA product isolated by chromatography on Sephadex LH-20 eluted with a methanol-water gradient is resolved into two separate components in a methanol-sodium borate solution gradient suggesting that, as is known for benzo(a)pyrene, two stereoisomeric diol-epoxides are involved in the binding of DMBA to DNA. 相似文献
8.
An SV40-based shuttle vector system was used to identify the types of mutational changes and the sites of mutation within the supF DNA sequence generated by the four stereoisomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide (B[c]PhDE), by racemic mixtures of bay or fjord region dihydrodiol epoxides (DE) of 5-methylchrysene, of 5,6-dimethylchrysene, of benzo[g]chrysene and of 7-methylbenz[a]anthracene and by two direct acting polycyclic aromatic hydrocarbon carcinogens, 7-bromomethylbenz[a]anthracene (7-BrMeBA) and 7-bromomethyl-12-methylbenz[a]anthracene (7-BrMe-12-MeBA). The results of these studies demonstrated that the predominant type of mutation induced by these compounds is the base substitution. The chemical preference for reaction at deoxyadenosine (dAdo) or deoxyguanosine (dGuo) residues in DNA, which is in general correlated with the spatial structure (planar or non-planar) of the reactive polycyclic aromatic hydrocarbon, is reflected in the preference for mutation at AT or GC pairs. In addition, if the ability to react with DNA in vivo is taken into account, the relative mutagenic potencies of the B[c]PhDE stereoisomers are consistent with the higher tumorigenic activity associated with non-planar polycyclic aromatic hydrocarbons and their extensive reaction with dAdo residues in DNA. Comparison of the types of mutations generated by polycyclic aromatic hydrocarbons and other bulky carcinogens in this shuttle vector system suggests that all bulky lesions may be processed by a similar mechanism related to that involved in replication past apurinic sites. However, inspection of the distribution of mutations over the target gene induced by the different compounds demonstrated that individual polycyclic aromatic hydrocarbons induce unique patterns of mutational hotspots within the target gene. A polymerase arrest assay was used to determine the sequence specificity of the interaction of reactive polycyclic aromatic hydrocarbons with the shuttle vector DNA. The results of these assays revealed a divergence between mutational hotspots and polymerase arrest sites for all compounds investigated, i.e., sites of mutational hotspots do not correspond to sites where high levels of adduct formation occur, and suggested that some association between specific adducts and sequence context may be required to constitute a premutagenic lesion. A site-specific mutagenesis system employing a single-stranded vector (M13mp7L2) was used to investigate the mutational events a single benzo[a]pyrene or benzo[c]phenanthrene dihydrodiol epoxide–DNA adduct elicits within specific sequence contexts. These studies showed that sequence context can cause striking differences in mutagenic frequencies for given adducts. In addition, these sequence context effects do not originate only from nucleotides immediately adjacent to the adduct, but are also modulated by more distal nucleotides. The implications of these results for mechanisms of polycyclic aromatic hydrocarbon-induced mutagenesis and carcinogenesis are discussed. 相似文献
9.
Nida Suhail Nayeem Bilal Shirin Hasan Ausaf Ahmad Ghulam Md. Ashraf Naheed Banu 《Cell stress & chaperones》2015,20(6):1023-1036
Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage. 相似文献
10.
We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties. 相似文献
11.
M W Chou G D Easton S K Yang 《Biochemical and biophysical research communications》1979,88(3):1085-1091
The 1- and 2-positions of 7,12-dimethylbenz[a]anthracene (DMBA) were thought not to be involved in biotransformation to 1,2-epoxide and 1,2-dihydrodiol because of steric hindrance from the 12-methyl group (Biochem. Biophys. Res. Commun. : 357–362, 1978). However, we have identified four 2-phenols as rat liver microsomal metabolites of DMBA and its methyl-hydroxylated metabolites, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]-anthracene, and 7,12-dihydroxymethylbenz[a]anthracene. Our findings suggest that neither the 12-methyl group nor the 12-hydroxymethyl group blocks the microsomal oxygenations of the 1,2 positions of DMBA or its methyl-hydroxylated derivatives. The 2-phenols may be formed as nonenzymatic rearrangement products of the 1,2-epoxide intermediates, although their formations by a direct hydroxylation mechanism cannot be ruled out. 相似文献
12.
In comparison with the fluorescence emission spectra of 7-methylbenz[a]-anthracene-nucleoside adducts, the fluorescence emission spectra of hydrocarbon-deoxyribonucleoside adducts containing a methyl substituent in the "bay region" lack spectral resolution at room temperature and appear at substantially longer wavelength. This spectral resolution is improved when spectra are measured at 77 K and an irreversible spectral shift to shorter wavelength, accompanied by improved resolution, results from mild acid hydrolysis. These spectral properties peculiar to the "bay region-substituted" adducts presumably result from an intramolecular interaction between the hydrocarbon fluorophore and the attached nucleoside brought about, in the examples studied here, by the presence of the 12-methyl group in 7,12-dimethylbenz[awanthracene (DMBA) and in 7-hydroxymethyl-12-methylbenz[a]anthracene. This interaction suggests that the site of nucleoside attachment is in close proximity to the 12-methyl group and that binding occurs, therefore, through the intermediacy of a 3,4-diol-1,2-oxide, i.e. a "bay region" diol-epoxide in each case. 相似文献
13.
14.
A close correlation has been observed between the ability of aromatic polycyclic hydrocarbons and 7,8-benzoflavone (7,8-BF) to induce hepatic aryl hydrocarbon hydroxylase (AHH) in vivo and to inhibit the induced enzyme system in vitro. The activity of this mono-oxygenase was measured by the conversion of 14C-labeled dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP) to water-soluble products by rat liver preparations (8000 X g supernatant). DMBA as substrate had the advantage over BP in giving a wider range of ethyl acetate-soluble metabolites and allowing the observation of changes in the pattern of these products following injection or addition of the inducing agents. This property was used to detect low concentration (0.1 muM) of polycyclic hydrocarbons which are strong AHH inducers and which may also be carcinogenic. The liver preparation was active for several months when stored at --20 degrees. A possible mechanism of action for the in vitro behaviour of polycyclic hydrocarbons and 7,8-BF towards AHH is proposed. 相似文献
15.
L M Thurmond A N Tucker D E Rickert L D Lauer J H Dean 《Chemico-biological interactions》1989,72(1-2):93-104
The metabolism of the polycyclic aromatic hydrocarbon (PAH) 7,12-dimethylbenz[a]anthracene (DMBA) was studied in murine lymphocytes. This carcinogen has previously been shown to be immunosuppressive to lymphocytes regardless of their ability to be induced via the Ah locus and receptor. Experiments were designed to quantify the generation of metabolites of DMBA by lymphocytes incubated with [14C]DMBA and to ascertain whether radioactivity was covalently bound to cellular macromolecules in DMBA-exposed lymphocytes. No significant metabolism of DMBA was detected in culture supernatants, except when cultures were incubated in the presence of Arochlor-induced rat liver 9000 x g supernatants (S9). Covalent binding of 14C to cellular macromolecules was enhanced approximately eightfold in the presence of S9. Inhibition of monooxygenase activity by alpha-naphthoflavone did not modulate the immunosuppressive character of DMBA. Furthermore, addition of S9 did not amplify or ablate DMBA-mediated suppression of lymphocyte proliferation to the mitogen concanavalin A (Con A). Selected metabolites of DMBA were evaluated for immunosuppressive effects in cultures stimulated with mitogens and cellular alloantigens. 7-Hydroxymethyl-12-methylbenz[a]anthracene (OHMe) and 5,6-dihydro-5,6-dihydroxybenz[a]anthracene (Diol) were found to cause only slightly greater suppression of lymphocyte responses than DMBA. Thus, it appears that metabolites of DMBA were not responsible for the immunosuppression observed in lymphocyte cultures and that lymphocytes were not equipped to metabolize any significant amount of DMBA. These data lend support to the hypothesis that parent compound alone is responsible for the immunosuppressive effects observed in murine lymphocyte culture. 相似文献
16.
M Shoyab 《Chemico-biological interactions》1979,25(1):71-85
A rapid procedure to study the interaction of carcinogens with DNA in cultured cells has been developed. The cells, which are labeled with 7,12-[3H]dimethylbenz[a] anthracene ([3H]DMBA), are lysed with 0.24 M phosphate buffer (pH 6.8), 1% sodium dodecyl sulfate (SDS), 8 M urea and 0.01 M ethylenediamine-tetraacetate (EDTA) and sonicated. The cell lysates are fractionated on columns of hydroxylapatite. Proteins and RNA are removed with 8 M urea in 0.24 M phosphate buffer (pH 6.8). DMBA-bound DNA is eluted with 0.4 M phosphate buffer (pH 6.8). DMBA-DNA isolated by this procedure is virtually free from proteins and RNA. Thermal stability, ultraviolet spectra and the density of DNA is not altered by DMBA binding. The uptake of DMBA by mouse epidermal cells is rapid and the binding of DMBA to DNA is linear for the first 8 h of exposure. DMBA binds to DNA in all phases of the cell cycle. However, the highest binding occurs immediately following maximum DNA synthesis. 相似文献
17.
Typically, chemopreventive agents either inhibit the cytochrome P450s (CYPs) that are essential for the metabolism of carcinogens or induce phase II detoxifying enzymes. This study examined the chemopreventive effect of eugenol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced DNA damage in MCF-7 cells. Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding. Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene. Therefore, eugenol has a potent protective effect against DMBA-induced genotoxicity, presumably through the suppression of the DMBA activation and the induction of its detoxification. These results suggest that eugenol has potential as a chemopreventive. 相似文献
18.
A system of cell-mediated mutagenesis is described for the study of compounds which require metabolic activation to exert their cytotoxic and mutagenic effects. This system combines BHK21 cells for metabolism of the compounds and V79 cells as targets for mutagenesis. Using the two polycyclic hydrocarbon carcinogenesis benzo(a)pyrene and 7-methylbenz(a)anthracene we have shown that the hydrocarbon-DNA reaction which accompanies mutagenesis in the target cell is indistinguishable from that reported to occur in vivo and in primary cell cultures. Our results also support the view that a diol epoxide metabolite is responsible for the biological activity of benzo(a)-pyrene.The application of cell-mediated mutagenesis to the routine testing of suspect environmental chemicals for biological activity is discussed. 相似文献
19.
David C. McMillan Peter P. Fu James P. Freeman Dwight W. Miller Dr. Carl E. Cerniglia 《Journal of industrial microbiology & biotechnology》1988,3(4):211-225
Summary Six strains of fungi grown on Sabouraud dextrose broth in the presence of 7,12-dimethylbenz[a]anthracene (DMBA) were surveyed for their ability to metabolize DMBA. Experiments with [14C]DMBA indicated that the extent of formation of organic-soluble metabolites ranged from 6 to 28% after 5 days of incubation, depending on the organism tested. The yields of water-soluble metabolites also varied, and ranged from 1 to 33% after 5 days.Cunninghamella elegans ATCC 36112 andSyncephalastrum racemosum UT-70 exhibited the highest DMBA-metabolizing activity among the organisms surveyed.S. racemosum metabolized DMBA primarily to 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA)_ and 7,12-dihydroxymethylbenz[a]anthracene (7,12-diOHMBA). Minor metabolites included 7-OHM-12-MBA-trans-5,6-, 8,9- and 10,11-dihydrodiols, and glucuronide and sulfate conjugates of phenolic derivatives of DMBA. In contrast, the major DMBA metabolites produced byC. elegans were water-soluble. The predominant organic-soluble metabolites produced byC. elegans included 7-OHM-12-MBA-trans-5,6-, 8,9- and 10,11-dihydrodiols. DMBA-trans-3,4-dihydrodiol was also detected. Circular dichroism spectral analysis revealed that the major enantiomer of the 7-OHM-12-MBA-trans-8,9-dihydrodiol formed by each organism has anS,S absolute configuration, while the major enantiomers of the 5,6-, 10,11- and 3,4-dihydrodiols had anR,R configuration. The mutagenic activity of extracts fromS. racemosum exposed to DMBA were determined inSalmonella typhimurium TA98. The mutagenicity of DMBA decreased by 36% over a period of 5 days as 33% of the compound was metabolized. Comparison of these results with previously reported results in mammalian systems suggests that there are similarities and differences between the fungal and mammalian oxidation of DMBA and that the overall balance of fungal metabolism is towards a detoxification rather than a bioactivation pathway. 相似文献
20.
Properties of 3-methyladenine-DNA glycosylase from Escherichia coli. 总被引:21,自引:0,他引:21
An Escherichia coli enzyme that releases 3-methyladenine and 3-ethyladenine in free form from alkylated DNA has been purified 2800-fold in 7% yield. The enzyme does not liberate several other alkylation products from DNA, including 7-methylguanine,O6-methylguanine, 7-methyladenine, N6-methyladenine, 7-ethylguanine, O6-ethylguanine, and the arylalkylated purine derivatives obtained by treatment of DNA with 7-bromomethyl-12-methylbenz[a]anthracene. The reaction of the enzyme with alkylated DNA leads to the introduction of apurinic sites but no chain breaks (less than one incision per ten apurinic sites), and there is no detectable nuclease activity with native DNA, depurinated DNA, ultraviolet-irradiated DNA, or X-irradiated DNA as potential substrates. The enzyme is termed 3-methyladenine-DNA glycosylase. It is a small protein, Mr = 19 000, that does not require divalent metal ions, phosphate, or other cofactors in order to cleave base-sugar bonds in alkylated DNA. 相似文献