Effects of the nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine on Salmonella typhimurium TA100 in the host-mediated assay in mice

The N-nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine (APNG) was examined for mutagenicity in the mouse host-mediated assay using Salmonella typhimurium strain TA100. Administration of APNG orally or as a single ip injection was shown to produce an increase in revertants. This study provides the first evidence that APNG is absorbed after oral administration in mice and demonstrates that the mutagenic product of APNG is short-lived in vivo.     

The in vivo genotoxic properties of the nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine

The N-nitrosopeptide N-(N-acetyl-L-prolyl)-N-nitrosoglycine (APNG) was investigated for in vivo genotoxicity using the dominant lethal assay and the micronucleus test in mice, and the bone marrow test in rats. APNG was shown to cause definite genetic effects in the mouse but a much lesser effect in the rat, indicating that APNG is a genotoxic agent in vivo.     

Mutagenic properties of N-nitrosopeptides in mammalian cell culture assays

Two N-nitrosopeptides, N-(N-acetyl-L-prolyl)-N-nitrosoglycine and N-(N-acetylvalyl)-N-nitrosoglycine, were investigated for genetic toxicity towards mammalian cells using an established line of Chinese hamster ovary cells (CHO-K1-BH4). Observations were made on three indices of genetic damage, namely chromosome aberrations, sister chromatid exchange and induction of thioguanine-resistant variants. Treatment of cells with either compound resulted in dose-dependent increases in all indices, indicating that both compounds are direct-acting mutagens.     

Mutagenicity of 2-hydroxyalkyl-N-nitrosothiazolidines

The mutagenicity of 2-hydroxyalkyl-N- nitrosothiazolidines was tested using Salmonella typhimurium strains TA98 and TA100. The N- nitrosothiazolidines tested were unsubstituted N- nitrosothiazolidine (NT), N- nitrosothiazolidine -4-carboxylic acid ( NTC ), 2-hydroxymethyl-N- nitrosothiazolidine ( HMNT ), 2-(1,2,3,4- tetrahydroxybutyl )-N- nitrosothiazolidine , 2-(1,2,3,4- tetrahydroxypentyl )-N- nitrosothiazolidine , 2-(1,2,3,4,5- pentahydroxypentyl )-N- nitrosothiazolidine ( PHPNT ) and 2-(1,2,3,4,5- pentahydroxypentyl )-N- nitrosothiazolidine -4-car boxylic acid. Among the N- nitrosothiazolidines tested, only HMNT and PHPNT exhibited clear dose-response mutagenicity toward strain TA100 with or without metabolic activation. None of the 2-hydroxyalkyl-N- nitrosothiazolidines were mutagenic to strain TA98. NT exhibited much stronger mutagenicity than either HMNT or PHPNT . Mutagenic activities of NT and PHPNT were eliminated by carboxyl substitution in the position alpha to the N-nitroso group.     

In vitro and in vivo genotoxic effects of somatic cell nuclear transfer cloned cattle meat

Although the nutritional composition and health status after consumption of the meat and milk derived from both conventionally bred (normal) and somatic cell nuclear transferred (cloned) animals and their progeny are not different, little is known about their food safeties like genetic toxicity. This study is performed to examine both in vitro (bacterial mutation and chromosome aberration) and in vivo (micronucleus) genotoxicity studies of cloned cattle meat. The concentrations of both normal and cloned cattle meat extracts (0-10×) were tested to five strains of bacteria (Salmonella typhimurium: TA98, TA100, TA1535, and TA1537; Escherichia coli: WP2uvrA) for bacterial mutation and to Chinese hamster lung (CHL/IU) cells for chromosome aberration, respectively. For micronucleus test, ICR mice were divided into five dietary groups: commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) normal cattle meat, and pellets containing 5% (C-5) and 10% (C-10) cloned cattle meat. No test substance-related genotoxicity was noted in the five bacterial strains, CHL/IU cells, or mouse bone marrow cells, suggesting that the cloned cattle meat potentially may be safe in terms of mutagenic hazards. Thus, it can be postulated that the cloned cattle meat do not induce any harmful genotoxic effects in vitro and in vivo.     

Mechanism-based inactivation of cytochrome P450 2B6 by a novel terminal acetylene inhibitor.

N-(3,5-Dichloro-4-pyridyl)-3-(cyclopentyloxy)-4-methoxybenzamide (DCMB) is a known marker substrate for cytochrome p450 2B6. Based on the chemical template of DCMB, a novel terminal acetylene compound, N-(3,5-dichloro-4-pyridyl)-4-methoxy-3-(prop-2-ynyloxy)benzamide (TA) was synthesized and evaluated as a mechanism-based inactivator of p450 2B6. The pseudo first-order inactivation of expressed p450 2B6 by TA was both substrate and time-dependent. The kinetics of inhibition resulted in a maximal rate constant (k(inactivation)) of 0.09 min(-1) and an apparent K(I) of 5.1 microM. Incubation of expressed p450 2B6 with TA and NADPH resulted in a 68% loss in enzyme activity and a concurrent 62% loss in the formation of a reduced carbon monoxide complex, suggesting that heme destruction is the primary mode of enzyme inactivation. Enzyme inactivation of p450 2B6 was not reduced by the presence of 10 mM glutathione and was protected by incubation of excess DCMB with TA. The production of the carboxylic acid metabolite, N-(3,5-Dichloro-4-pyridyl)-3-(2-carboxyethoxy)-4-methoxybenzamide (TA-COOH), during the incubation of TA with 2B6 suggests that inactivation proceeds through a ketene intermediate. For 2B6 inactivation, the partition ratio was approximately 1.5 nmol TA-COOH formed/nmol P450 inactivated. Finally, TA was evaluated for mechanism-based inactivation of p450 3A4, 2C9, 2C19, 2D6, and 2E1 using human liver microsomes. In addition to 2B6, p450 2C forms were also found to be sensitive to TA-mediated inactivation, suggesting that subtle changes in the O-alkyl chain of the parent may be critical for the selectivity of enzyme inactivation.     

Atypical molecular pharmacology of a new long-acting beta 2-adrenoceptor agonist, TA 2005.

The molecular pharmacology of a new putative long-acting bronchodilator TA 2005 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxy-phenyl)- 1-methylethyl]amino]ethyl]carbostyril hydrochloride) has been compared with that of the reference compounds isoprenaline and salbutamol in both methacholine (3 x 10(-6) M) precontracted guinea pig tracheal smooth muscle relaxation and in bovine trapezium muscle binding experiments. TA 2005 appeared very potent compared with isoprenaline and salbutamol (pD2 values of 9.29 vs. 7.65 and 7.10 respectively). For isoprenaline and salbutamol a shallow displacement curve was observed and addition of the non-hydrolysable GTP analogue guanylyl-imidodiphosphate (GppNHp) gave a rightward shift (pKd,high and pKd,low values of 7.3 and 6.1 vs. 7.0 and 5.4 respectively). For TA 2005 a steep displacement curve was found with only one binding state even without GppNHp (pKd,high value of 8.2). The long duration of action of TA 2005 might be explained by tight binding of this compound to the beta 2-adrenoceptor. The extent of tight binding for TA 2005 was extremely large. The molecular basis of the tight agonist binding phenomenon for TA 2005 seems to be of different origin than for isoprenaline. It is hypothesized that a different mechanism of activation of the beta 2-adrenoceptor may be involved for TA 2005.     

Mutagenicity of some monoaromatic hydroxamic acids

The mutagenicity of some monoaromatic hydroxamic acids was tested in the presence and absence of rat liver S-9 with Salmonella typhimurium tester strains TA98 and TA100. Of the five N-(chlorophenyl)-substituted hydroxamic acids and seven N-arylformohydroxamic acids tested, 2 of the first and 4 of the latter series were mutagenic to both strains upon metabolic activation. None of the four N-acetyl-type hydroxamic acids was mutagenic to either strain, even upon activation. Because some of the N-acetyl-derived hydroxamic acids were inactive, whereas the same aromatic nucleus possessing a formyl group displayed significant activity, a consideration of the nature of the aryl group in hydroxamic acid mutagenicity is important.     

Effect of nitrofurylpropenylidene benzhydrazides against trichomonads, bacteria, yeasts and fungi with particular consideration of the results in the Ames test and host-mediated assay

11 out of 13 N-[3-[5-nitrofuryl-(2)-propenylidene)]-benzhydrazides described by us showed an in vitro activity against T. vaginalis almost equivalent to or approaching that of the standard substances metronidazole and tinidazole. One compound was markedly more effective; two compounds exhibited much weaker activity than the two reference substances. In the model of the T. foetus infection of mice, only two compounds came close to the chemotherapeutic effect of tinidazole when administered orally. The other compounds were less effective. Metronidazole showed an activity 10 times weaker than that of tinidazole in this animal model. The in vitro efficacy of the most active substances a and d on T. foetus infection paralleled the bacteriostatic effect against different species of bacteria. In comparison, d was more effective than a against T. vaginalis, 2 Candida strains and M. tuberculosis. In the Ames test, 5 out of the 13 described N-[3-[5-nitrofuryl-(2)-propenylidene))]-benzhydrazides proved mutagenic in test strains TA 98 and TA 100; this was the case also in strain TA 1537 for the microbiologically most promising compound a. Because of liver damage observed in the test on toxicity, the substance was not taken up in clinical studies. It is interesting to note that these substances were not found to be mutagenic in the host-mediated assay. No signs of chromosome breaks were observed for substances a and n in the micronucleus test. The relevance of these findings was discussed. Statistical procedures were described for both the Ames test and the host-mediated assay.     

The mutagenicities of seven coumarin derivatives and a furan derivative (nimbolide) isolated from three medicinal plants

Seven coumarin derivatives (imperatorin, heraclenin, xanthotoxin, marmesin, chelepin, oxypeucedanin, esculin) and a furan derivative (nimbolide) were screened on 6 Ames tester strains (TA92, TA94, TA97, TA98, TA100, TA102). The eight compounds are chemicals isolated from three Nigerian medicinal plants: Afraegle paniculata, Clausena anisata, and Azadirachta indica. Different preparations of the former are taken by Nigerians for gut disturbances, and a concoction of the latter called "Agbo" is taken as an antimalarial. Marmesin and imperatorin were mutagenic in all tester strains except TA94 and TA102. The mutagenicity potencies of marmesin and imperatorin were 20 and 0.2 respectively. Mutagenicity was highest in TA98 and TA100 in both compounds. Marmesin was optimally mutagenic at a dose of 1.04 micrograms, and imperatorin at 30.0 micrograms. Microsomal activation was not required for mutagenicity in both compounds.     

A critical evaluation of the present status of toxicity of aminoxyl radicals.

The literature on the toxicity of aminoxyl radicals was critically reviewed. It was concluded that, in general, the aminoxyl radicals possess a very low toxicity and are not mutagenic. In support of this contention, several aminoxyl radicals were evaluated in vitro. Thus, aminoxyl radicals 3-carboxy-2,2,5,5-tetramethylpyrroline-1-oxyl (1), 3-carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCA; 2), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol;3), and N-(1-hydroxymethyl-2,3-dihydroxypropyl)-3-carboxyamino-2,2,5,5- tetramethylpyrrolidine-1-oxyl (NAT; 4) were evaluated using Salmonella typhimurium tester strains TA 102 and TA 104, with a supplement of xanthine oxidase enzyme. 1, 2, and 4 were found to be nonmutagenic, while 3 elicited in TA 104 only about a twofold increase in the number of revertants above the control. This response is considered to be, at best, marginal in view of wide fluctuations of experimental scores. The results of the present study are in agreement with those of other studies confirming the nonmutagenicity of aminoxyl radicals investigated to date. However, these conclusions are different from those of a study where 3 was tested in the presence of a generated toxic oxygen species that can cause mutagenic changes of the environment.     

Mutagenic activity of cytostatic methyl hydrazones with different strains of Salmonella typhimurium.

Experiments are performed to ascertain the mutagenic properties of four new cytostatic methyl-hydrazones in the Ames test using different strains of Salmonella typhimurium. As could be demonstrated all four hydrazones are mutagenic per se without a metabolic activation through rat liver microsomes (S-9 fraction). Whereas the beta-chloroethyl hydrazones B1 and B2 cause a base-pair substitution with the strains TA100 and TA1535 the methyl-hydrazones EB4 and CyB4 both cause base-pair substitution with TA100 and frameshift mutation with TA98. At both strains the mutagenic activity of Cy84 ist powerful. Furthermore, no relation could be detected between the mutagenic properties of the methyl-hydrazones and their alkylating behaviour on 4-(4-nitrobenzyl)-pyridine.     

Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability

The influence of the proportion of acrylamidomethyl-gamma-cyclodextrin (gamma-CD-NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. gamma-CD-NMA was synthesized by condensation of gamma-cyclodextrin (gamma-CD) with N-(hydroxymethyl) acrylamide. Hydrogels were prepared with gamma-CD-NMA and sodium acrylate (3 M or 4 M), using N,N'-methylen(bisacrylamide) (BIS) as cross-linker, by free radical polymerization into glass moulds of 2 mm wide and were cut as discs (10 mm diameter). gamma-CD-NMA did not modify the pH-dependent swelling of the hydrogels, but significantly increased the swelling degree in the 40:60 ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with gamma-CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without gamma-CD-NMA. This is explained by the formation of 1:1 inclusion complexes of TA with gamma-CD mers that overcomes the lack of interactions with the acrylic groups of the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer was sustained for at least 24 h, whatever the pH and the composition of the medium used. In contrast, loading of PR from the water solutions was greater for hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to their content in gamma-CD-NMA, and in less than 2 h ca. 80% PR was released. The lower affinity of PR for the gamma-CD cavities, compared to the strong intensity of the electrostatic interactions with the acrylic acid groups, explains why the incorporation of gamma-CD-NMA did not increased the loading and control release capacity of the hydrogels of this hydrophilic drug. In summary, the copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH-sensitive networks which load large amounts of hydrophobic drugs and release them in a sustained way.     

Microbial transformation of the antihistamine pyrilamine maleate. Formation of potential mammalian metabolites

Fourteen fungi were found to metabolize pyrilamine (2-[(2-dimethylaminoethyl)(p-methoxybenzyl)amino]pyridine). Two Cunninghamella elegans strains transformed essentially all of the pyrilamine added after 144 hr. After 48 hr of incubation, C. elegans ATCC 9245 metabolized 76% of the antihistamine into methylene chloride-extractable pyrilamine metabolites. These organic-soluble metabolites were isolated by HPLC and the major metabolites were characterized by comparison of their chromatographic, mass, and 1H-NMR spectral properties with those of authentic compounds. The major metabolite was identified as 2-[(2-dimethyloxyaminoethyl)(p-methoxybenzyl)amino]pyridine (N-oxide derivative of pyrilamine). Other metabolites identified were 2-[(2-dimethylaminoethyl)(p-hydroxybenzyl)amino]pyridine, 2-[(2-methylaminoethyl)(p-methoxybenzyl)amino]pyridine, and 2-[(2-methylaminoethyl)(p-hydroxybenzyl)amino]pyridine. These metabolites represent O-demethylated, N-demethylated, and O- and N-demethylated derivatives of pyrilamine, respectively. The mutagenic activities of the N-oxide and the N- and O-dealkylated pyrilamine derivatives, and pyrilamine maleate were measured by reversion of Salmonella typhimurium strains TA97, TA98, TA100, and TA102. Pyrilamine maleate and the three microbial metabolites showed no appreciable mutagenic activity in any of the S. typhimurium tester strains. The metabolism of pyrilamine by 12 other filamentous fungi and yeast strains was much less when compared to C. elegans and ranged from 3.8% to 12.2%. The fungal metabolism of pyrilamine may be useful in predicting results of mammalian metabolism and in readily providing sufficient quantities of metabolites for further toxicological studies.     

Correlations of nitrenium ion selectivities with quantitative mutagenicity and carcinogenicity of the corresponding amines

There is a correlation (r(adj)(2) = 0.5491-0.6338) of quantitative mutagenicity, log m, for a series of heterocyclic (HCAs) and carbocyclic (AAs) aromatic amines in Salmonella typhimurium TA 98 (18 amines) and TA 100 (15 amines) vs log S, the log of the azide/solvent selectivity of the corresponding nitrenium ion. Monocyclic aromatic amines, MAAs, are less mutagenic than other amines of similar log S. Multiple variable linear regression analysis led to a two parameter regression model, significant at the 95% confidence level for both variables, that includes log S and a ring index variable, I(rings), that is 0 for MAAs and 1 for all other amines. These models have r(adj)(2) = 0.8448 for TA 98, and 0.8927 for TA 100. Inclusion of a third variable, Clog P, increases r(adj)(2) to 0.8913 for TA 98 and 0.9011 for TA 100. This model is significant at the 95% confidence level for all variables for TA 98, but only for two of the three variables for TA 100. The confidence level is 80% for Clog P in TA 100. Quantitative carcinogenicity data in mice and rats are more weakly correlated with log S (r(adj)(2) = 0.5357 for 12 amines in mice, r(adj)(2) = 0.4216 for 10 amines in rats). Several two parameter regression models, all containing Clog P and one containing log S, adequately correlate the mouse data.     

Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes

Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5-Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins both required intact microsomes, NADPH and O2 and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P-450. Microsomal oxidation of an isomer of tienilic acid (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P-450-dependent monooxygenases and is almost completely inhibited in the presence of sulfur containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P-450-dependent reaction. They also show that two thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding: stable metabolites ratio (4 instead of 0.5).     

Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid

The purpose of the present experiment was to examine the effects of D-tartaric acid (TA) on intestinal drug absorption under both in situ and in vitro experimental conditions. In the in vitro diffusion chamber experiments, TA (10 mM) added to the mucosal side of rat colon significantly decreased rhodamine123 (Rho 123) transport from the serosal to mucosal side. Since TA has been shown to change the integrity of the epithelial tight junctions in rat colon at low pH conditions, resulting in improved paracellular drug transport, the effect of TA on membrane resistance was examined at pH 7.4 in the present study. It was found that membrane resistance, an indicator of paracellular integrity, did not change at pH 7.4. In the in situ loop method, TA (20 mM) increased the absorption of Rho123 in both ileum and colon but not in jejunum. TA (20 mM) also increased the absorption of daunorubicin in the ileum, but TA (20 mM) did not change the expression level of P-glycoprotein (P-gp). TA (20 mM) significantly inhibited excretion of i.v.-administered Rho123 and daunorubicin into the ileal lumen. In conclusion, for the first time we demonstrated that TA increases the intestinal absorption of P-gp substrates Rho123 and daunorubicin, possibly by modulating the P-gp function without changing the expression level of P-gp in the rat intestine.     

Short-term dermal toxicity and mutagenicity of coal coprocessing products in the rat.

The present study was conducted to determine the dermal toxicity of coal coprocessing products and to assess their potential health hazards. Groups of 10 male and 10 female Sprague-Dawley rats were administered dermally coal coprocessing products (light gas oil, LGO; heavy gas oil I, HGOI; heavy gas oil II, HGOII) at 1 g/kg body weight/d for 14 d. The control and positive control groups received normal saline and a coal liquefaction product (CLP) at the same dose level, respectively. Treatment with either the three fractions of coprocessing products or CLP caused decreased growth rate and food consumption in animals of both sexes. Liver enlargement occurred in groups treated with HGOI, HGOII, and CLP. Decreased serum glucose was observed in animals of both sexes treated with the three fractions and CLP. Treatment with HGOI and CLP caused an elevation of hepatic microsomal ethoxyresorufin deethylase activity in the rat of both sexes. The three fractions and CLP caused mild anemia. Mild treatment-related histological changes were observed in the liver, spleen, thyroid, bone marrow, and kidney. All three fractions of coprocessing products were tested for their mutagenicity in five strains of Salmonella typhimurium: TA98, TA100, TA1535, TA1537, and TA1538. HGOI, after metabolic activation, was found to be mutagenic in the strains of TA98, TA100, and TA1538. In contrast, HGOII was mutagenic in the five strains with or without metabolic activation. These data indicate that HGOI and HGOII are more toxic than LGO, and should be subjected to further studies to determine their long-term effects.     

Mutagenicity of industrial wastewaters collected from two different stations in northern India

Mutagenicity of wastewaters taken from two different cities was compared by means of Ames plate test and Ames fluctuation test. TA100 and TA98 strains of S. typhimurium exhibited the highest sensitivity against the Saharanpur sample (SWW) in terms of the slope (m) of the dose-response curve in the plate incorporation assay. However, the most sensitive strain against the test samples from Aligarh (AWW) was TA98. Interestingly, TA100 and TA98 strains also displayed the highest susceptibility towards the samples from Saharanpur in the fluctuation test. However, TA102 and TA100 responded maximally to AWW in this bioassay. Interestingly, S9 supplementation resulted in the decline in mutagenic potential of SWW contrary to significant increase with AWW by both the tests. Both samples were found to generate different types of ROS as predominant species. While SWW were shown to generate a high concentration of superoxide radicals and hydrogen peroxide, hydroxyl radicals were predominantly occurring in AWW. From our result, we conclude that both the test water samples were highly genotoxic. In view of the complementary nature of these two testing systems, we recommend both bioassays for the genotoxicity assessment of complex water samples.     

Growth inhibition of intestinal bacteria and mutagenicity of 2-, 3-, 4-aminobiphenyls, benzidine, and biphenyl.

2-Aminobiphenyl (2-ABP), 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP), but not benzidine (Bz) and biphenyl (Bp), were found to be inhibitory to the growth of human intestinal bacteria Bifidobacterium infantis ATCC 15697, B. bifidium ATCC 11863, Clostridium perfringens ATCC 13124, Escherichia coli ATCC 25922, E. coli ATCC 35218, Enterobacter cloacae ATCC 13047 and Salmonella typhimurium TA98, TA100, YG1041 at 10-200 microg/ml in culture broth. Bacteroides distasonis ATCC 8503, B. fragilis ATCC 25285, B. theataiotaomicron ATCC 29741, C. paraputrificum ATCC 26780, C. clostridiiforme ATCC 25537, Lactobacillus acidophilus ATCC 4356 and Enterococcus faecium ATCC 19434 were not inhibited by the above mentioned compounds in concentrations up to 200 microg/ml. The Ames Salmonella/microsome assay was employed to test the mutagenicity of the above-mentioned compounds using strains TA98 and TA100 in the presence and absence of Aroclor 1254-induced rat S9 mix. It was found that 4-ABP was mutagenic to both TA98 and TA100, and Bz was mutagenic to TA98 in the presence of rat S9 mix. 2-Aminobiphenyl, 3-ABP, and Bp were not mutagenic to both strains tested. 2-Aminobiphenyl and 3-ABP are chemical isomers of 4-ABP and are as strong as 4-ABP in inhibiting the growth of intestinal bacteria but not as mutagenic as 4-ABP. Evidence suggested that the mechanism of growth inhibition is not involved with the interaction of DNA that causes mutations, but rather on the electron transport system of these organisms.