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1.
Three naturally occurring indoles were evaluated for potential nitrosatability using the Nitrosation Assay Procedure (NAP test) as recommended by the World Health Organisation. All three indoles i.e. tryptophan, tryptamine and 5-hydroxy-tryptamine were nitrosated to products which were directly mutagenic for S. typhimurium TA1537. In addition, the products of nitrosation of tryptamine and 5-hydroxytryptamine were also mutagenic for strains TA1538, TA98 and TA1535 without the need for metabolic activation. The sensitivities of the frameshift-detecting strains TA1537, TA1538 and TA98 were of particular interest, since nitroso compounds are characteristically base-substitution mutagens. The mutagenic effects of the products formed after nitrosation of each indole at pH 3.6, were eliminated in the presence of S9 mix. This was not the case when the nitrosation assay was carried out at pH 2.6. At this pH the mutagenicity of the nitrosated products varied in the presence of S9 mix and depended upon the nature of the indole undergoing nitrosation, and the bacterial test strain utilised for the mutagenicity assay. This indicated that more than one mutagenic product was responsible for the observed effects. As well as pH, a number of other factors influenced the formation of mutagenic nitroso products. Most notably, the concentrations of precursor compounds (sodium nitrite, and indole) present in the NAP test were of critical importance. As the sodium nitrite concentration was reduced from that recommended by the W.H.O. (40 mM), so the mutagenicity decreased. For all three compounds significant mutagenic effects were lost at sodium nitrite concentrations below 15 mM. In conclusion the data presented in this paper clearly demonstrates that individuals are chronically exposed to naturally occurring substances which readily nitrosate in excess nitrous acid and yield bacterial mutagens.  相似文献   

2.
The genotoxic potential of bidi tobacco was evaluated by mutagenicity testing of aqueous, aqueous: ethanolic, ethanolic and chloroform extracts of processed tobacco used in the manufacture of 'bidis', indigenous forms of cigarettes smoked in India. The Salmonella/mammalian microsome test (Ames assay) was used to detect mutagenicity in tester strains TA98, TA100 and TA102. The extracts were tested in the absence and presence of metabolic activation using liver S9 from rat and hamster, and following in vitro nitrosation with sodium nitrite at acidic pH. All the extracts were non-mutagenic in the absence of nitrosation. The nitrosated aqueous extract was mutagenic in strains TA98 and TA100. While weak mutagenicity was elicited by the nitrosated aqueous: ethanolic extract in TA100, the nitrosated ethanolic extract induced a 3-fold increase in the number of revertants in the same strain. Moreover both these extracts elicited a strong mutagenic response in TA102, while the chloroform extract was non-mutagenic even after nitrite treatment. The present study indicates that workers employed in the bidi industry are exposed to potentially mutagenic and genotoxic chemicals in the course of their occupation.  相似文献   

3.
Mutagenicities of indole and 30 derivatives after nitrite treatment   总被引:4,自引:0,他引:4  
Indole and 7-derivatives, L- and D-tryptophan and 9 derivatives, and beta-carboline (norharman) and 11 derivatives were tested for mutagenicity to Salmonella typhimurium TA100 and TA98 after nitrite treatment. 1-Methylindole, which is present in cigarette smoke condensate (Grob and Voellmin, 1970; Hoffmann and Rathkamp, 1970), was the most mutagenic to TA100 without S9 mix after nitrite treatment, inducing 615,000 revertants/mg. 2-Methylindole, 1-methyl-DL-tryptophan, harmaline and (-)-(1S,3S)-1,2-dimethyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid also showed strong mutagenicity after nitrite treatment, inducing 129,000, 184,000, 103,000 and 197,000 revertants/mg, respectively. These mutagenic potencies were comparable with those of benzo[alpha]pyrene, 3-methylcholanthrene and 2-amino-9H-pyrido[2,3-b]indole (A alpha C) (Sugimura, 1982). Of 31 compounds tested, 22 were mutagenic after nitrite treatment. Since various indole compounds are ubiquitous in our environment, especially in plants, the presence of their mutagenicities after nitrite treatment warrants further studies, including those on their in vivo carcinogenicities.  相似文献   

4.
Apomorphine, N-nor-N-propyl-apomorphine, dopamine, L-DOPA, 6-hydroxydopamine and adrenaline were evaluated for genotoxicity using the Ames test and DNA repair-deficient and DNA repair-proficient Bacillus subtilis strains (rec assay, H17/M45; HLL3g/HJ-15). In the absence of an S9 liver homogenate, apomorphine induced frame-shift mutations in Salmonella typhimurium, mainly in strain TA1537; no indication of DNA-damaging effects in B. subtilis was observed. N-Nor-N-propyl-apomorphine was tested using strain TA1537 only and found to be mutagenic. Dopamine, L-DOPA, 6-hydroxydopamine and adrenaline were non-mutagenic when tested without S9, whereas they were all more toxic for DNA repair-deficient than for DNA repair-proficient B. subtilis strains, indicating a DNA-damaging potential. In a second set of experiments the mode of action of apomorphine and the relevance of the positive Ames test data were investigated. Glutathione in physiological concentrations reduced the mutagenic effect of apomorphine in a dose-dependent way, both in the presence and the absence of S9. S9 also reduced the mutagenicity of apomorphine. By comparing the effects of a complete S9 mix with those of a preparation without glucose-6-phosphate and NADP, it became clear that S9 also had an activating effect, overshadowed under standard conditions by its deactivating activity. Apomorphine was not mutagenic under anaerobic conditions. Superoxide dismutase and catalase reduced the mutagenic effect of apomorphine. All test conditions which reduced the mutagenic effect also inhibited the dark discoloration of the tester plates, indicating a retardation of apomorphine oxidation. It can, therefore, be concluded that oxidation of apomorphine leads to mutagenic products which induce frame-shift mutations in Salmonella typhimurium. This oxidation was prevented both by glutathione in concentrations well below physiological levels and/or by catalase and superoxide dismutase. Under these conditions, apomorphine was non-mutagenic in therapeutic concentrations as well as at higher dose levels. The possibility of genotoxic side effects occurring in patients treated with apomorphine as an emetic drug is therefore considered to be very unlikely.  相似文献   

5.
Mutagenicity of 6-aminoquinoxaline derivatives was tested with Salmonella typhimurium strains Ta98 and TA100 in the presence and absence of S9 mix from the viewpoint that the 6-aminoquinoxaline skeleton is a common unit of mutagenic imidazoquinoxalines. We tested nine compounds: 5-methyl-6-methylaminoquinoxaline (1), 3,5-dimethyl-6-methylaminoquinoxaline (2), 2,5-dimethyl-6-metnylaminoquinoxaline (3), 6-methylamino-2,3,5-trimethylquinoxaline (4), 2,3-diethyl-5-methyl-6-methylaminoquinoxaline (5), 5-methyl-6-methylamino 3-phenylquinoxaline (6), 6-amino-2,3,5-trimethylquinoxaline (7), 6-dimethylamino-2,3-5-trimethylaminoquinoxaline (8), 6-amino-2,3-dimethylquinoxaline (9). These compounds showed the mutagenic activity for both TA98 and TA100 in the presence of S9 mix, where they were more sensitive for TA100 strain. Methyl groups at the 2, 3 and/or 5 positions increased the potency of mutagenicity (1 < 2 < 3 ⪡ 4, 9 < 7). However, ethyl groups at the 2 and 3 positions lowered the mutagenicity of the methyl substitute but elevated it of the parental compound (1 < 5 < 4). A methyl group at the N6 position decreased the mutagenicity (7 > 4 > 8).  相似文献   

6.
The mutagenicity of cigarette smoke condensate (CSC) was investigated in Neurospora crassa in the presence and absence of S9 mix prepared from Aroclor-1254-induced rat liver. CSC from the University of Kentucky Reference Cigarette 1R1 was assayed in a forward-mutation test at the adenine-3 (ad-3) region in resting conidia of 2-component heterokaryons. In the absence of S9 mix, CSC exhibited direct-acting mutagenicity. CSC was also mutagenic in the presence of S9 mix, but higher doses were required than in the absence of S9 mix. The dose range, survival curves, and mutation-induction curves were not significantly different when CSC was used in the presence of unheated or heat-inactivated S9. There was a positive association between killing and mutagenicity, and CSC killed conidia of N. crassa by a cytoplasmic, rather than by a nuclear, mechanism. The mutagenic potency of CSC was similar in a repair-sufficient and a nucleotide excision repair-deficient heterokaryon of N. crassa. CSC did not exhibit a photodynamic effect for killing, and CSC caused more killing at high pH than at low pH. In addition, CSC caused more killing at 37 degrees C than at 25 degrees C and also caused more killing in higher concentrations (20%) of solvent (DMSO) than in low concentrations (1%). This is the first report of the presence of potent direct-acting mutagens in CSC.  相似文献   

7.
The fried food mutagens IQ, MeIQ, Glu-P-1 and Trp-P-2 were treated with nitrite at pH 3.0 for 1 h at 37 degrees C. The resulting reaction mixtures were tested for mutagenicity towards Salmonella typhimurium TA97, TA98, TA100 and TA1535. Glu-P-1 and Trp-P-2 were readily converted to weak or non-mutagenic deaminated compounds, whereas IQ and MeIQ were converted to extremely strong mutagenic derivatives in both the presence and the absence of rat liver S9 mix. The mutagenicity of MeIQ in TA98 was enhanced by nitrite up to 3-fold, while that of nitrosated MeIQ was further enhanced by S9 mix up to 15-fold. The nitrosation products of MeIQ were resolved into 7 bands by TLC on silica gel plate. Bands I, III, V and VI were highly mutagenic to both TA98 and TA100. The experimental results suggest that the non-enzymatic formation of direct-acting mutagens from indirect-acting mutagens such as IQ or MeIQ might be physiologically important, especially with regard to the etiology of human gastrointestinal tract tumors.  相似文献   

8.
The coccidiostat diaveridine was tested for mutagenicity in the Salmonella/microsome assay with tester strains TA100 and TA98. This compound was not mutagenic in either tester strain in the presence and absence of rat S9 mix, but was found to be mutagenic in strain TA100 after metabolic activation with hamster S9 mix.  相似文献   

9.
Extracts of pure cotton and jeans fabrics were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100. The vat dye indigo, technical grade as well as 98% and greater than 99.5% pure, was also tested for mutagenicity. Synthetic indigo, indirubin and isatin were tested for TCDD receptor affinity in competition experiments in vitro. The mutagenicity of the extracts was associated with the cotton denim and nondyed cotton gave only marginal effects. The mutagenicity of the indigo dyed fabrics was dependent on type and treatment of the fabrics. Extracts of both bleached and nonbleached jeans gave mutagenic effects on TA98 +/- S9 and TA100 +/- S9. The greatest effects were seen in the presence of S9. Bleaching gave an additional increase in the mutagenicity in the absence of S9. Normal washing of the fabrics after bleaching reduced the mutagenicity. Synthetic indigo of technical grade or 98% pure showed mutagenic effects, especially on TA98 + S9. Further purification to 99.5% reduced the mutagenicity to 24 revertants/mg (6.2 rev/mu mole). Considering the amount of indigo in the extracts and its low mutagenicity, the genotoxicity of jeans extracts must be caused by other unknown components. However, indigo showed a high (Kd = 1.9 nM) affinity for the Ah or TCDD receptor. Indigo can therefore still be a potential health risk either by eliciting toxic effects of other compounds or by being a nongenotoxic carcinogen. The worldwide use of jeans with a possible exposure of a large population to genotoxic and biologically active components emphasizes the need for a more thorough characterization of these effects.  相似文献   

10.
The mutagenic effect of 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) was compared with that of the 3-amino, 3-nitro, or 3-N-hydroxylated derivatives of the same base ring with methyl groups at positions 4 and 6 of the molecule. The compounds were tested in Salmonella typhimurium strain TA98 without metabolic activation and in the presence of different concentrations of subcellular fractions from livers or small intestines of rats pretreated with different P448/P450 inducers. The 4,6-dimethyl compounds are always more mutagenic than Glu-P-2. Pretreatment with Aroclor 1254 (ARO) is the most effective inducer in the activation of the 2- and 3-amino compounds by liver S9, whereas the same fraction decreases the mutagenicity of the 3-nitro derivative. S9 from small intestine increased the mutagenic effect of the 3-nitro and 3-N-hydroxylated compounds, but it was unable to activate the amino compounds.  相似文献   

11.
The mutagenic potential of three alkyl 2-cyanoacrylate adhesives, three commercial alkyl 2-cyanoacrylate adhesives and three methyl 2-cyano-3-phenylacrylates, was assessed using the Salmonella/microsome mutagenicity assay. Compounds were tested with and without Aroclor 1254-induced rat-liver homogenate (S9 mix). The methyl 2-cyanoacrylate adhesives were mutagenic in the standard plate test with S. typhimurium strain TA100 with and without S9 activation. Methyl 2-cyano-3-(2-bromophenyl)acrylate revealed a direct mutagenic action to S. typhimurium strain TA1535. The compounds most toxic towards the bacterium S. typhimurium, were the methyl 2-cyanoacrylate adhesives (greater than 500 micrograms/plate). All alkyl 2-cyanoacrylate adhesives were tested in a modified spot test for volatile compounds with tester strain TA100. Mutagenic and toxic effects were observed with the three methyl 2-cyanoacrylate adhesives. It can be concluded from the results that the bacterial toxicity and mutagenicity of methyl 2-cyanoacrylate adhesives may be due to the methyl 2-cyanoacrylate monomer.  相似文献   

12.
The mutagenicity of the base analogue, 2-amino-N6-hydroxyadenine (AHA), was tested in Salmonella typhimurium TA100 and TA98 and in Chinese hamster lung (CHL) cells. AHA showed very potent mutagenicity in TA100 without S9 mix, inducing 25,000 revertants/micrograms. The mutagenicity increased about 2-fold upon addition of S9 mix containing 10 microliters S9. AHA was found to be one of the strongest mutagens for TA100. Addition of S9 mix containing 100 microliters S9 induced no significant increase of revertants with AHA at amounts up to 50 ng per plate. AHA was also mutagenic for the frameshift mutant, TA98, without S9 mix, the mutagenicity for TA98 being about 1/1000 of that for TA100. When the mutagenicity of AHA was tested in CHL cells, with diphtheria toxin resistance (DTr) as a selective marker in the absence of S9 mix with a 3-h treatment of cells, DTr mutants increased dose-dependently at concentrations of 2.5-15 micrograms/ml. When cells were incubated with AHA for 24 h, a 200-fold increase in the number of DTr mutants was observed; the mutagenicity was 500-fold higher than that of ethyl methanesulfonate. This marked increase of mutagenicity by prolonged incubation may indicate that AHA induces mutations mainly after incorporation into DNA. The addition of a small amount of S9 increased the mutagenicity obtained with a 3-h treatment 2-fold, but a larger amount of S9 decreased the mutagenicity as was found with S. typhimurium TA100.  相似文献   

13.
The mutagenicity of 7 positional isomers of aminoquinolines (AQ) and their N-acetyl derivatives (AcAQ) was tested in Salmonella typhimurium TA100 and TA98 in the presence and absence of S9 mix. In a series of aminoquinolines, the order of mutagenic potency in the presence of S9 mix is: 5-AQ greater than 8-AQ greater than 7-AQ greater than 3-AQ greater than 2-AQ much greater than 4-AQ, 6-AQ. The alpha-positional isomers, 5-AQ and 8-AQ, are more mutagenic than the beta-isomer, 2-, 3-, 6-, 7-AQ's. These results are in contrast to the finding that beta-naphthylamine is more mutagenic than alpha-naphthylamine. In a series of N-acetylaminoquinolines, the order of mutagenic potency in the presence of S9 mix is: 7-AcAQ greater than 6-AcAQ greater than 8-AcAQ much greater than all the others. It is suggested that the AQ and AcAQ series might exert their mutagenicity through different molecular mechanisms (i.e., metabolic activation) from each other. The rate of metabolic activation does not seem to be correlated with the mutagenic potency of the compounds. It is noteworthy that 7-AQ and 8-AQ are mutagenic in both the strains tested in the absence of S9 mix.  相似文献   

14.
Wood combustion produces compounds that are mutagenic in the Salmonella/microsome assay. As combustion products can be emitted in the home and the use of wood as a residential energy source is growing, an impact on human health might be of concern. In this study experiments were carried out to determine the contribution of wood combustion in stoves and fire places to indoor mutagenic activity under normal living conditions. Airborne particles from living rooms which were heated by stoves, or by fire places, and from outdoors were collected simultaneously. In each room two samples were collected during two consecutive weeks: one week the room was heated by central heating, the other week by wood combustion. Sampling took place in a total of 24 homes. Methanol extracts of the samples were tested in the Salmonella/mammalian microsome assay. Results show that mutagenic activity of outdoor air exceeds indoor mutagenicity. At the same time a correlation is found between in- and out-door mutagenicity, both with and without S9. However, a large difference is found between the ratio -S9/+S9 of in- and out-door mutagenic activity. Systematic differences in the ratio -S9/+S9 between control and experimental conditions are not observed. The use of wood stoves caused an increase of indoor mutagenicity in 8 out of 12 homes. It could be concluded that the use of an open fire consistently leads to an increase of mutagenic activity. This increase was caused by wood combustion products.  相似文献   

15.
1-Nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP), 1-6-dinitropyrene (1,6-DNP), 1,8-dinitropyrene (1,8-DNP) and 1,3,6-trinitropyrene (1,3,6-TNP) were tested for mutagenicity in cultured Chinese hamster ovary (CHO) cells. Mutation at the hypoxanthine-guanine phosphoribosyl transferase gene locus was quantified. While 1-NP and 1,3-DNP had only marginal direct-acting mutagenicity, 1,6-DNP, 1,8-DNP and 1,3,6-TNP showed definite mutagenicity, with specific mutagenic activities of 8.1, 21 and 54 mutants/10(6) survivors/micrograms . ml-1 respectively. The mutagenicity of 1-NP increased with increasing concentrations of Aroclor-1254 induced liver homogenate (S9) in the treatment medium. However, S9 at all concentrations tested decreased the mutagenicity of 1,6-DNP and 1,8-DNP. S9 at low concentrations enhanced the mutagenicity of 1,3-DNP and 1,3,6-TNP and that at high concentrations decreased their mutagenicity. The positive mutagenic response of the nitropyrenes suggests that they are potentially carcinogenic, and that further research into their possible human health risk should be performed.  相似文献   

16.
Four antitumoral 5,8-quinazolinediones were examined for their ability to induce mutation in Salmonella typhimurium. Each compound was tested at several concentrations in 4 strains. Relationships were established between the structure of the quinones and their mutagenic activities. The mutagenicity was influenced by (i) the nature of the substituent(s) of the quinonic moiety: the methoxyquinone had no mutagenic properties and the aziridinylquinones were mutagenic in the 4 strains with or without activation by S9 mix; (ii) the presence or the absence of a diaminopolymethylenic chain in the 4 position; (iii) the monomeric or the dimeric structure of the tested compound. Interestingly, the data indicated that the aziridinylquinazolinedione bearing the dimethylaminopropylamino chain in the 4 position was less mutagenic and had greater antitumor activity than the dimeric quinone.  相似文献   

17.
The mutagenicity of nifurtimox (nfx) and 8 nfx analogues has been investigated with the L-arabinose forward-mutation assay of Salmonella typhimurium. The nfx analogues tested were obtained by replacing the 3-methyl-4-yl-tetrahydro-1,4-thiazine-1,1-dioxide group of the parent compound with the following other groups: indazol-1-yl (1); pyrazol-1-yl (2); benzimidazol-1-yl (3); 1,2,4-triazol-4-yl (4); 1-methyl-3-methylthio-1,2,4-triazol-4-yl-5-thione (5); 3,5-bis(methylthio)-1,2,4-triazol-4-yl (6); 1-adamantyl (7); 4,6-diphenylpyridin-1-yl-2-one (8). The mutagenic activity of each chemical was determined by the standard plate-incorporation test, in the presence or absence of the S9 activation mixture. The 9 compounds were mutagenic and exhibited linear dose-mutagenic response relationships. They were direct-acting mutagens and showed a nearly 1000-fold range in mutagenic potency from chemical 1 to nfx. In most cases, the addition of S9 mixture to the test plates decreased the mutagenicity of compounds. This effect was particularly noticeable in the case of chemicals 1-3, 5 and 7 where a more than 70% decrease in mutagenic activity was observed in the presence of the S9 mixture. The mutagenic potency of compounds in the Ara test showed a negative linear correlation with previously reported antitrypanosomal activity. Thus, chemicals 6 and 8 with in vitro activities against Trypanosoma cruzi clearly superior to that of nfx showed 2 of the lowest mutagenic potencies in the Ara test and these were only somewhat higher than the mutagenicity of the reference drug.  相似文献   

18.
Methyl isocyanate (MIC) was tested for mutagenicity using the Ames Salmonella/microsome liquid-preincubation procedure with slight modification of test conditions. In the modification the preincubation mixture was incubated at 10 degrees C for 60 min. MIC was assayed both in the presence and absence of Aroclor-1254-induced S9, using 5 tester strains of Salmonella typhimurium, TA97a, TA98, TA100, TA102 and TA104. MIC induced mutagenic response in two base-pair substitution strains, TA100 and TA104, in the presence and absence of S9. However, mutagenic response in the presence of S9 was low as compared to that in the absence of S9. In the comparative mutagenic activity at 3 different preincubation test conditions (37 degrees C for 20 min, 20 degrees C for 40 min and 10 degrees C for 60 min), optimum mutagenic response was observed at 10 degrees C for the 60-min test condition. However, no mutagenic response was observed at 37 degrees C for the 20-min test condition.  相似文献   

19.
Ten imidazole derivatives were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 both in the absence and presence of metabolic activation by the microsomal fraction S9 mix. In a general manner, derivatives tested exhibited a greater mutagenic activity in the TA100 strain comparing to the responses in TA 98. In the standard plate incorporation assay, 8 of these substances (80%) were found to be mutagenic for at least one of the two strains in the presence or absence of metabolic activation. Two compounds showed positive results in TA98 and 6 compounds were also mutagenic in TA100 without S9. In the presence of S9 mix, all of the 10 substances were non-mutagenic in TA98, whereas 4 compounds were positive in TA100. The results suggested the mutagenic potentials of the imidazole derivatives particularly inducing the reversion of base-pair substitutions. According to the structure-activity relationships phenyl groups in position 2 with different substituents can confer the mutagenic activity of the tested compounds. Methyl groups in different positions of these phenyl substituents can cause different types of mutations. This mutagenic effect is observed more clearly when the phenyl group is inhibited with a nitro group.  相似文献   

20.
Four pyrazolones in frequent use, i.e. antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests. In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively. When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100. The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N. Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N. In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite. No mutagenicity was detected with the reaction mixture (IPA-N) in either strain.  相似文献   

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