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(CANCER RESEARCH 49, 6600-6604, December I, I989| Antimutagenic Effects of in a Bacterial Assay System1

Stewart A. Laidlaw,2 Marian F. Dietrich, Maria P. Lamtenzan, HernánI. Vargas, Jerome B. Block, and Joel D. Kopple

Departments of Medicine fS. A. L., M. F. D., M. P. L., H. I. V., J. B. B., J. I). K.] and Public Health [S. A. L., J. D. K.J. Schools of Medicine and Public Health, llarhitr- VCLA Medical Center and the University of California Los Angeles, Terranee, California 90509 and I.os Angeles, California 90024

ABSTRACT ven, CT), danthrone and MNNG3 (Sigma). GES was kindly supplied by Dr. Ryan Huxtable. Taurine (2-aminoethanesulfonic acid) was evaluated as an antimu- Histidine-requiring mutant strains of Salmonella typhimurium were tagen in the Ames Salmonella tester strain assay. Taurine inhibited obtained from Dr. Bruce Ames. Several strains with sensitivity to mutagenesis by doxorubicin (-74%), bleomycin (-55%), mitomycin specific types of mutational events were used. Strain TA98 primarily C (—56%), and 2-aminofluorene (—52%), but not danthrone or detects frameshift mutations (10); strain TA 100 detects base pair sub benzo(a)pyrene, in strain I \ 102. In strain TA98, doxorubicin mutagen- stitution mutations (10), and strain TA 102 is particularly sensitive to icity, but not that of 2-aminofluorene or ben/o(a)pyrene, was inhibited mutations caused by oxidative damage (11, 12). The S9 microsomal by taurine. A'-Methyl-/V'-nitro-A'-nitrosoguanidine (-73%), but not fraction of homogenized rat liver was isolated by standard techniques dexon, mutagenicity was inhibited by taurine in strain TA100. Taurine (13, 14) and was included in assays of mutagens which require biological inhibited those mutagens against which it was effective in a dose-related activation to produce their mutagenic effects. fashion. Taurine was more effective in inhibiting doxorubicin mutagen The methods used in these studies were those described by Ames and icity in strain TA 102 than its analogues hypotaurine, /3-, and coworkers. Briefly, the tester strains to be used in the assay were grown guanidinoethanesulfonic acid or alanine or . The observed inhibi overnight in Oxoid nutrient broth (Difco Laboratories, Detroit, Ml) in tion may indicate a role for taurine in modulating the activity of oxidant an Orbit Environ-shaker (Lab-line, Melrose Park, IL). Compounds to species. be assayed for mutagenesis were mixed with 0.1 ml of the nutrient broth culture of bacteria, 0.5 ml of rat liver S9 mixture (when appro priate), and 2 ml of molten (45°C)top agar and immediately overlaid INTRODUCTION on Vogel Banner E Medium minimal glucose (2% w/v) plates contain Taurine (2-aminoethanesulfonic acid) is found in all tissues ing minimal liistilline (15), as described by Levin et al. (11). The plates were allowed to harden in the dark and were incubated inverted for 48 and biological fluids in animals and often is present in high h at 37°Cin a humidified incubator (Wedco, Inc., Silver Spring, MD). (HIM) concentrations ¡ntracellularly. Apart from its role as a Under the conditions described, there is a certain background level of conjugator of bile acids (1), its biological functions remain spontaneous revenants to the histidine-independent wild type. The poorly understood. Taurine has been implicated as a stabilizer degree of mutagenicity in response to a specific mutagenic agent is of excitable membranes (1, 2), an osmoregulatory agent (3), calculated as the number of revenants above the background level. and a modulator of neurotransmission (4). Recently, Wright et Revertan! colonies were counted using an Artek Model 880 plate al. (5) suggested that taurine may act as a general detoxifier for counter (Artek Systems, Farmingdale, NY). The range of concentra oxidant compounds, reacting with and removing chemically tions used for a given mutagen were chosen, on the basis of preliminary active free radical species. These species are generated at high testing, to produce the optimal mutagenic effect with minimal toxicity. rates in certain organs and cells, such as the heart, retina, and The toxicity of the compounds tested was assessed by whether the neutrophils, and can cause extensive chemical damage to , number of spontaneous revenant colonies, in the presence of the proteins, carbohydrates, and nucleic acids. Taurine is present compound, fell in comparison to the number of colonies observed in in high concentrations in these cells and tissues (5, 6-8). the absence of the compound. Taurine or other amino acids, when Several known or suspected carcinogenic agents may cause present, were added to the tester strains at the same time as the mutagenic changes in DNA by promoting formation of reactive mutagen. free radical species (9). We therefore began a series of studies The effect of taurine on the mutagenicity of the various mutagens to examine whether taurine may protect against free radical- tested was examined both over a range of mutagen concentrations and at several different taurine concentrations. The effect of taurine on each induced cellular damage. In this study, we used the Ames mutagen was assayed in separate experiments. Each combination of Salmonella bacterial assay system to assess the ability of taurine taurine and mutagen was examined using duplicate plates, and the net to reduce the mutagenic capacity of various known carcinogens. number of revenants reported is the average of these duplicate plates minus the average number of spontaneous revenants. In each assay series, duplicate plate incubations were performed in parallel to the test MATERIALS AND METHODS plate incubations to confirm the mutagenic sensitivity of the tester Chemicals were obtained as follows: taurine (U.S. Biochemical Cor strain used (using a standard mutagen) and to check for toxicity of the poration, Cleveland, OH); glycine, alanine. fi-alanine, and hypotaurine vehicles (water or dimethyl sulfoxide) used to administer the mutagen (Sigma Chemical Co., St. Louis, MO); doxorubicin (Adriamycin; Adria and/or taurine or other amino acids. In addition, at frequent intervals, Laboratories, Columbus, OH); bleomycin (Mead Johnson, Evansville. incubations were performed to confirm the phenotypic characteristics IN); mitomycin C (Bristol-Meyers, Syracuse, NY); benzo(a)pyrene and of each tester strain. The characteristics evaluated were the histidine 2-AF (Aldrich Chemical, Milwaukee, WI); dexon (Analabs. New Ha- requirement, the incidence of spontaneous reversion, the continued exhibition of ampicillin resistance, confirmation of the rfa character, Rcccived 6/13/89; revised 8/16/89; accepted 9/5/89. indicating a partial loss of the bacterial lipopolysaccharide barrier, by The costs of publication of this article were defrayed in part by the payment crystal violet sensitivity (13), and of continued sensitivity to UV light, of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. indicating the absence of a functioning uvrßgene, a functional loss 1Supported by IR01 DK33112 (to J. D. K.). the UCLA Clinical Nutrition characteristic of the strains used (16). Research I'nit 5P01 CA427IO (to S. A. L., J. B. B.), and Eisenhower Medical Data were expressed as (a) the net number of revenants per plate Center. Rancho Mirage. CA (to H. I. V.). Some of the data in this paper were presented at the Annual Meeting of the Federation of American Soeicties for (i.e., the measured number of revenant colonies in the presence of the Experimental Biology. Las Vegas. NV, in May 1987. tested substance minus the number of spontaneous revenants) or (/>) 1To whom requests for reprints should be addressed, at Division of Nephrology and Hypertension. Harbor-UCLA Medical Center. 1000 W. Carson Street. ' The abbreviations used are: MNNG, A'-methyl-.V'-nitro-.V-nitrosoguanidine; Terranee. C'A 90509. 2-AF, 2-aminofluorene: GES. guanidinoethanesulfonic acid. 6600

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600 the percentage inhibition of reversion, i.e., o— ono tau •—«tau,50mg/plate Rm ~ Rm x 100 500 * »tau,10mg/plate 3 * »tau,1mg/plate .0- 400-• where Rmis the number of revenants in the presence of a mutagen and R„,is the number of revenants in the presence of the mutagen and taurine or other tested compound.

RESULTS •00 Taurine itself produced no toxic or mutagenic effects with Adriamycin (/¿g/plate) any bacterial tester strain examined; this was observed with Fig. 1. Effect of increasing concentrations of taurine (tau) on the dose response taurine concentrations from 50 to 50,000 /¿g/plate.As reported of revenants to increasing doses of doxorubicin in Strain TA 102. The scale of previously (17-20), mutagenicity was observed for doxorubicin the abscissa is logarithmic (range, 10-100 ^g doxorubicin/plate); the scale on the (Adriamycin), bleomycin, mitomycin C, 2-AF, dexon, dan- ordinate is arithmetic. Net revertants/plate refers to the number of revenant bacterial colonies observed in the presence of the mutagen minus the number of throne, and benzo(a)pyrene in appropriate strains. The degree revertan! colonies observed when no mutagen was added. Data points represent of mutagenicity observed was dose dependent for each mutagen. the mean of duplicate plate determinations. The figure is representative of the results obtained in several (at least two) replications of the experiment. Using bacterial strain TA 102, the mutagenicity of doxorubi cin, bleomycin, mitomycin C, and 2-aminofluorene was inhib 800 ited by taurine in a dose dependent manner (Table 1; Figs. 1- o—o no tau • «tau,10000ug/p 3). The inhibition tended to be greater at lower concentrations 700 »—»tau,5000ug/p 600 » »tau,1000ug/p of the mutagen and sometimes was not evident at higher mu a otau, 500ug/p tagen levels and/or lower taurine concentrations. The maxi 500 mum inhibitions observed were: doxorubicin, 74%; bleomycin, 55%; mitomycin C, 56%; and 2-AF, 52% (Table 1). In general, as the amount of taurine added to the plates increased, the net number of revenants induced by each of these four mutagens decreased. For some concentrations of these mutagens, the degree of inhibition tended to be linear with the log of the 1E-1 taurine content of the plate. At doxorubicin concentrations of 15-100 /¿g/plate,taurine Bleomycin (/¿g/plate) concentrations of 5,000 ^g/p'ate or greater invariably inhibited Fig. 2. Effect of increasing concentrations of taurine on the dose response of the net number of revenants caused by doxorubicin. Taurine revenants to increasing doses of bleomycin. The scale of the abscissa is logarithmic [range. 0.1-5.0 ^g bleomycin/plate (p)]- the scale on the ordinate is arithmetic. concentrations of 1,000 ßgtaurine/plate or greater inhibited Net revertants/plate refers to the number of revenant bacterial colonies observed the net number of revenants observed at all bleomycin concen- in the presence of the mutagen minus the number of revenant colonies observed when no mutagen was added. Data points represent the mean of duplicate plate Table 1 Effect of taurine on mutagenicity of Adriamycin, bleomycin, mitomycin, determinations. The figure is representative of the results obtained in several (at 2-AF, and danthrone in bacterial strain TA 102 least two) replications of the experiment. Net no. of revertants/plate6 at following 2000 concentration of taurine (^g/plate) o ono tau • «tau,10000ug/p MutagenDoxorubicinBleomycinMitomycinS9±°100302015102.5 »—»5000ug/p a 1500-. » «1000ug/p a o500ug/p

+1.0 500- +0.5 +0.25 +2.5

C2-AFDanthroneplate+1.0 +0.5 Mitomycin C (¿ig/plate) +0.1 +25020015(110(150105101398f9037423923557936213992981855138110984976717466485151823081352050011666645903725075053420129617701466921269443561525421291297197431.0001190795516379506654891802548191024989270320559480496355291127335,000116353841726804873691981669434339852284964135404393582791723410,000849340322100513582972351701555614964230528489620449355ND"NDNDFig. 3. Effect of increasing concentrations of taurine on the dose response of revenants to increasing doses of mitomycin C. The scale of the abscissa is arithmetic [range, 0.1-2.5 ¿igmitomycin C/plate (/?)]; the scale on the ordinale is arithmetic. Net revertants/plate refers to the number of revenant bacterial colo nies observed in the presence of the mutagen minus the number of revenant colonies observed when no mutagen was added. Data points represent the mean of duplicate plate determinations. The figure is representative of the results obtained in several (at least two) replications of the experiment.

trations from 0.25 to 2.5 jug/plate. Mitomycin C mutagenicity " Incubations performed in the absence (-) or presence (+) of rat liver S9 was inhibited at all concentrations tested (0.1-2.5 Mg/p'ate) by microsomal mix. taurine concentrations of 1,000 /ug/plate or greater. For 2-AF 4 Revenant colonies in plates incubated with mulagen minus revenant colonies concentrations of 150. 200, and 250 ¿ig/plate,mutagenicity in in plates incubated without mutagen. c Mean of duplicate plates. strain TA 102 was inhibited by taurine concentrations of 500- rfND. not done. 10,000 ¿ig/p'ate.However, taurine had no effect on mutagen- 6601

Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 1989 American Association for Cancer Research. TAURINE AND MUTAGENESIS icity induced by 2-AF at 50 ^g/plate. 1200 In contrast, the mutagenicity of danthrone (Table 1), dexon, or benzo(a)pyrene (data not shown) was not inhibited progres sively by increasing taurine concentrations, nor were the lower concentrations of these mutagens more sensitive to inhibition by taurine than higher levels of the compounds (data not shown). In strain TA98, which is sensitive predominantly to frame- shift mutations, taurine (1,000-50,000 /ug/plate) inhibited the mutagenic effects of doxorubicin, whereas the mutagenicity of 2-AF or benzo(a)pyrene was essentially unaffected by taurine 100 1000 1E4 concentrations of 500-5,000 /ug/plate (Table 2). Benzo(a)py- Taurine concentration (ug/plate) rene in concentrations of 20 and 50 ¿(g/platemay have been Fig. 4. Effect of increasing concentrations of taurine on the dose response of slightly inhibited by taurine. Higher concentrations of taurine revenants at differing doses of MNNG. The scale of the abscissa is logarithmic were not tested with 2-AF or benzo(a)pyrene. Using strain [range. 20-50.000 ng taurine/plate (/))]; the scale on the ordinate is arithmetic. Net revertants/plate refers to the number of revenant bacterial colonies observed TA 100, which is sensitive to base pair substitution mutations, in the presence of the mutagen minus the number of revenant colonies observed the mutagenicity of the rat colon carcinogen MNNG was inhib when no mutagen was added. Data points represent the mean of duplicate plate determinations. The figure is representative of the results obtained in several (at ited by taurine; the inhibitory effects of taurine increased in a least two) replications of the experiment. linear fashion as the taurine concentrations rose logarithmically

(Table 3; Fig. 4). The maximum inhibition observed was 73% 125 at 50,000 Mgtaurine/plate with 10 mivi MNNG/plate. In con trast, taurine (500-5,000 Mg/p'ate) did not appear to affect the mutagenicity of dexon in this tester strain (Table 3). & 100 The antimutagenic properties of taurine were compared with two common «-aminoacids (glycine, alanine), and three struc ¿ 75- tural analogues of taurine (hypotaurine, 0-alanine, and GES).

The amounts of each added to these assays were ir, 50 •• 100-10,000 Mg/plate (0.5-267 ^mol/plate). Each level of each amino acid was tested two to six times. Doxorubicin (30 Mg/

100.0 Table 2 Effect of taurine on Adriamycin, hen:o(a)pyrene, and 2-aminofluon-ne mutagenicity in bacterial strain TA 98 Amount added (micromoles/plate) no. of revertants/plate* at follow ing Fig. 5. Comparison of the effects of laurine and other amino acids on doxo rubicin mutagenicity. The scale on the abscissa is logarithmic (0.5-300 ^mol/ (^g/plate)0400Cconcentrations of taurine plate for individual amino acids): the scale on the ordinate is arithmetic. Net MutagenAdriamycinMC/plateS9±"7.5 rcvertants/plate refers to the number of revenant bacterial colonies observed in the presence of the mutagen minus the number of revertan! colonies observed - when no mutagen was added. Data points represent the mean of duplicate plate 5.0Net 302500ND''N D1,0002972525.00027912310.00025914450.000192160 determinations. The figure is representative of the results obtained in several (two to six) replications of the experiment over various ranges of concentrations of 2-AF 20 + 1416 1534 1316 1416 ND ND amino acijs. Doxoruhicin. 30 ^g/platc. was present in all incubations. 10 + 1019 963 1107 953 ND ND 2 + 392 404 473 309 ND ND plate) and increasing concentrations of these amino acids were Benzo(fl)pyrenc 200 + 212 185 175 255 ND ND 100 + 237 259 227 242 ND ND incubated with strain TA 102. Taurine was a more effective 50 + 282 215 231 240 ND ND inhibitor of doxorubicin mutagenesis in this assay than any 20 + 267 237 216 190 ND ND other amino acid tested (Fig. 5). As the concentrations of amino " Incubations performed in the absence (-) or presence (+) of rat liver S9 acid used increased, all amino acids studied eventually showed microsomal mix. * Revenant colonies in plates incubated with mutagen minus revenant colonies some inhibitory effect. The taurine analogues, /j-alanine and in plates incubated without mutagen. GES, however, were only effective at rather high concentra c Mean of duplicate plates. rfND. not done. tions. Hypotaurine and alanine showed apparent strong inhi bition of mutagen-induced revenant colony formation at higher

Table 3 Effect uf taurine on MNN(J and de.ton mutagenicity in bacterial strain concentrations; these amino acids, however, inhibited the num TA 100 ber of spontaneous revenants observed in control plates at these Net no. of revertants/plate* at follow ing same higher concentrations, suggesting that they were exhibit (^g/plate)MutagenMNNGDexonMg/plateconcentrations of taurine ing a toxic effect on bacterial growth, which was unrelated to S9±"10.07.55.0 any antimutagenic effect. Once a concentration of a given amino acid was attained that inhibited doxorubicin-induced muta genesis, further increases in the amino acid concentrations -502510501079C4706686980136320250102043399ND"NDNDND10089744391NDNcaused greater suppression of mutagenesis in a roughly loga rithmic fashion (Fig. 5). The concentrations of amino acid that DN caused a 50% inhibition of doxorubicin mutagenesis are shown DND500874499779448243822081.000851391348257744842075.0007623774082481644818710.00061033822NDNDNDND50,000288"M20NDNDNT)NDin Table 4. By this measure, taurine was twice as potent as ' Incubations performed in the absence (-) or presence (+) of rat liver S9 glycine. 3 times more potent than hypotaurine. 6 times more microsomal mix. effective than alanine. 15 times more inhibitory than ¿-alanine. * Revenant colonies in plates incubated with mutagen minus revenant colonies and 28 times more potent than GES. It should be emphasized in plates incubated without mulagen. ' Mean of duplicate plates. that these relationships are only approximate because of the ''ND. not done. small number of concentrations of each amino acid tested. 6602

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Table 4 Intimated concentration o/ amino m'iti that inllihits iloxanihicin-inditcctl inhibited the mutagenicity of doxorubicin (TA98, TA102), bleo mutagenesis by 50% mycin (TA 102). mitomycin C (TA 102), 2-aminofluorene umol/platc (TA102), and MNNG (TA100) by up to 74% in a dose-depend Taurine 5.9 ent manner over a range of mutagen concentrations. The ob Glycine 12.7 Hypouiurine 18.3 served inhibition was approximately linear over the entire con Alaninc 31.5 centration range studied with any particular concentration of GES 92.8 mutagen. In contrast, 2-AF (TA98). danthrone (TA 102), .^-.Manine 168.5 benzo(a)pyrene (TA98, TA 102), and dexon (TA 100) mutagen icity were essentially unaffected by taurine. Although doxorub DISCUSSION icin inhibition by taurine was seen with strain TA98 (Table 2), Some carcinogens are thought to act by causing oxidative the most pronounced effect was observed with strain TA 102, a damage (9, 21). Doxorubicin (Adriamycin) and mitomycin C strain engineered to detect oxidative mutations (Table 1; Fig. are believed to undergo metabolic activation to free radicals 1). (18). These free radicals may interact with oxygen, either di Although in the Ames Salmonella tester strain assay, the rectly or indirectly, to generate oxgyen radical species via su- intracellular environment in which mutagenic events occur may peroxide anión formation. This may eventually lead to the be quite different from that existing in mammalian cells, the production of hydrogen peroxide (18). Bleomycin forms a fer assay has proven successful in identifying chemical carcinogens rous iron-bleomycin complex which may react with oxygen to (10-14, 16, 17). It has been used extensively to screen a wide generate Superoxide anión, also leading to hydrogen peroxide array of compounds for mutagenicity (17). Since there is a high formation (22). The mutagenicity of these three compounds degree of correlation between known carcinogenicity and mu (doxorubicin, mitomycin C, and bleomycin) in the Ames bac tagenicity in the Ames test, chemicals identified as mutagens terial assay system can be inhibited by incubation with either by this method have been implicated as potential carcinogens Superoxide dismutase or catalase; combining Superoxide dis- in animals (14). In this or other systems (18, 31), some of these mutase and catalase was more effective in reducing mutagenesis putative carcinogens have been proposed to produce chemical than was either enzyme alone (18, 23). These data suggest that species which could produce oxidative damage to the bacterial some mutagenesis may be due to reactive oxygen species and/ DNA base sequence, either directly or by promoting formation or hydrogen peroxide generation. More recently, 2AF and of other oxidative agents. A number of putative benzo(o)pyrene have also been shown to cause generation of compounds, including K, (menadione), vitamin C, and hydrogen peroxide in vitro (24, 25). In contrast, dexon and vitamin E, have been demonstrated to reduce the level of danthrone may act by other mutagenic mechanisms. mutations produced in the Ames assay by these potential oxi The role of taurine as a major intracellular molecule (e.g., 20 dative mutagens (18, 23). Similarly, Superoxide dismutase and/ mmol/liter intracellular water or greater (5-8)) remains ob or catalase inhibit the formation of mutant colonies in this scure, despite intensive investigation over many years. Recently, assay (23). it has been proposed that taurine may act as a general detoxifier Taurine inhibited formation of revertant colonies most effec of oxidative species (5). Cauli et al. (26) demonstrated that the tively in a strain of Salmonella bacteria which was selected to presence of taurine in culture medium increases the viability of be sensitive to mutations caused by oxidative damage (TA 102). lymphoblastoid cell lines. They also showed that these and The maximum extent of inhibition observed was generally 50- other cell types could elaborate A'-chlorotaurine, a condensation 60%. If taurine acts as an antioxidant, this suggests either that product of taurine and hypochlorous acid, the latter being a not all mutational events which occur in this strain may result potent oxidative species (27-29). They speculated that this from oxidative damage or that taurine may not completely condensation system might exert a protective effect on the cell; inhibit oxidative damage, even at concentrations of taurine as conjugation with taurine could remove oxidative species capable high as 50,000 /ug/plate. Taurine also inhibited mutagenesis in of reacting with and damaging various intracellular compounds, strains (TA98, TA 100) not specifically designed to detect oxi such as nucleic acids, proteins, and carbohydrates (5). Similarly, dative mutations. This may reflect either a nonantioxidant bile acids conjugated with laurine are less toxic to endothelial function of taurine or a minor sensitivity to oxidative damage cell cultures than the equivalent free bile acids (5). Taurine may in these strains. Similarly, taurine inhibited mutagenesis by also play a role in maintaining cell membrane stability by virtue mutagens not reported to produce oxidative damage (MNNG). of its ability to interact with potent oxidizing agents (5). In Again, in this case taurine may act by a nonantioxidant-based vitro studies, in contrast, have not demonstrated that taurine mechanism, or MNNG may have an unreported ability to cause can directly interact with various oxidant and free radical spe oxidative damage. cies (30). When the specificity of the antimutagenic actions of taurine We tested the effectiveness of taurine as an antimutagen was assessed by comparing its effectiveness with several other using a variety of Salmonella tester strains and the mutagens amino acids, including several structural analogues, fi-alanine doxorubicin, bleomycin, mitomycin C, 2-aminofluorene, and GES were poor inhibitors of mutagenesis. Hypotaurine, benzo(a)pyrene, dexon, MNNG, and danthrone. All mutagens the closest structural analogue of taurine, although more potent were incubated with those bacterial strains which had previously than /i-alanine or GES, was still about 3 times less potent than been shown to be sensitive to their effects. We tested the effect taurine. Hypotaurine, as well as alanine, appeared to be toxic of taurine at various concentrations from 50 to 50,000 ^g/plate, to the bacteria at higher doses; thus the ability of these two a 1,000-fold range of concentrations (not all concentrations amino acids to inhibit mutagenesis could be assessed only over were studied with all mutagens). Taurine itself was not muta a narrower concentration range than taurine. Within that range genic, nor was it toxic in concentrations up to 50,000 /jg/plate. taurine was a more effective inhibitor of doxorubicin mutage This relative nontoxicity of taurine may be another reason why nesis. Surprisingly, glycine may have been almost as effective exceptionally high concentrations of this amino acid are found as taurine (Fig. 5). Our data suggest that the antimutagenic in animal cells (5-8). Using various tester strains, taurine effect of taurine is relatively specific and may be an intrinsic 6603

Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 1989 American Association for Cancer Research. TAURINE AND MUTAGENESIS property of the structure of taurine. The specific mode of action 14. Ames. B. N.. Durston. W. E.. Yamasaki. E., and Lee, F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation of taurine as an antimutagenic agent remains to be elucidated and bacteria for detection. Proc. Nati. Acad. Sci. USA. 70: 2281-2285. 1973. but it is interesting to speculate that it may involve the neutral 15. Vogel, H. J..and Bonner. D. M. Acetyl ornithinaseof Escherichia coli: partial purification and some properties. J. Biol. Chem.. 218: 97-106. 1956. ization, either directly or indirectly, of some type of free radical 16. Ames. B. N.. Lee. F. D.. and Durston, \\. E. An improved bacterial test or oxidative species. system for the detection and classification of mutagens and carcinogens. Proc. Nati. Acad. Sci. USA. 70: 782-786, 1973. 17. McCann. J.. Choi, E.. Yamasaki, E.. and Ames. B. N. Detection of carcino gens as mutagens in the Sa/mon