Antimutagenic effect of Phellinus rimosus (Berk) Pilat against chemical induced mutations of histidine dependent Salmonella typhimurium strains

Mutations are one of the important factors contributing to oncogenesis. Somatic mutations have been detected in oncogenes and tumor suppressor genes in various types of cancers. In vitro antimutagenic activity of ethyl acetate extract of macro fungus, Phellinus rimosus was evaluated by Ames’ mutagenicity assay. The effect was evaluated against the direct acting mutagens (sodium azide, N-methyl-N′-nitro-N-nitrosoguanidine, doxorubicin and 4-nitro-o-phenylenediamine) and mutagen needing activation (2-acetyl aminofluorine, and benzo[a]pyrene). The extract was significantly (p < 0.05) and dose dependently effective against direct acting mutagens and mutagen needing activation. Among the antimutagenic activity against directly acting mutagens, effect was found to be highest against doxorubicin-induced mutation. The antimutagenic effect of the extract against indirect acting mutagen in the presence of mammalian metabolic activation system was also found to be significant (p < 0.01). The background bacterial growth and number of revertant colonies in the extract alone treated plate with or with out metabolic activator was almost same as that of spontaneous revertants. This indicated the non-toxic nature of the extract. The effect was partially ascribed to the antioxidant activity. The results of the study suggest the possible antitumor mechanisms of P. rimosus.     

Cytotoxicity,mutagenicity, and antimutagenicity of the gentisic acid on HTC cells

Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic activities. This substance can be found in citrus fruits, grapes, olive oil, and peas. Considering that there are few studies in the literature on the toxicity of GA, the present work aimed to investigate its cytotoxic, mutagenic, and antimutagenic activities on HTC cells. GA was diluted in culture medium at the final concentration of 0.08, 0.16, 0.8, 1.6, and 8?μg/mL. The cytotoxicity was determined by the MTT assay and Trypan Blue exclusion method, with methyl methanesulfonate and doxorubicin as positive controls, respectively. The cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic activity with benzo[a]pyrene as positive control. Negative control received culture medium only. GA (0.08–8?μg/mL) was not cytotoxic to HTC cells by the MTT assay nor the Trypan Blue exclusion method as no statistical difference was observed when compared to the control. Concentration of 0.08 and 0.8?μg/mL showed no mutagenic or clastogenic effects, as no significant micronuclei inductions were observed, different from 8?μg/mL, that was mutagenic. Furthermore, none of the concentrations presented an antiproliferative activity. The antimutagenic activity of GA (0.08?μg/mL) was observed at the simultaneous treatment, as it reduced the frequency of micronuclei by 76% (24?h) and 79% (48?h). Although pre- and post-treatments were not statistically different from the mutagen, they reduced the induced-damage by 11% and 21%, respectively. The present study indicated the absence of cytotoxicity and antiproliferative activities of GA, in addition to their antimutagenic/protective effects that may contribute to human health.     

IN VITRO INHIBITION OF CARCINOGEN-INDUCED MUTAGENICITY BY CASSIA OCCIDENTALIS AND EMBLICA OFFICINALIS

Aqueous extracts of Cassia occidentalis Linn. (Leguminoceae) and Emblica officinalis Gaertn. (Euphorbiaceae) were screened for effectiveness in inhibiting mutagenicity of aflatoxin B₁ (AFB₁) and benzo[a]-pyrene (B[a]P) in the Ames test. Antimutagenicity was evaluated using Salmonella typhimurium strains TA 98 and TA 100. In the assay, metabolic activation of AFB₁ (0.5 μg/plate) and B[a]P (1 μg/plate) was mediated by rat liver S9 preparation. Although both plants inhibited mutagenicity, E. officinalis had more inhibitory effect than C. occidentalis. Their action is possibly mediated through interactions with micro somal activating enzymes. Their inhibitory action on chromosomal aberrations together with present results suggest that these plants have potent antimutagenic and anticarcinogenic activities against mutagens requiring metabolic activation.     

In vitro inhibition of carcinogen-induced mutagenicity by Cassia occidentalis and Emblica officinalis

Aqueous extracts of Cassia occidentalis Linn. (Leguminoceae) and Emblica officinalis Gaertn. (Euphorbiaceae) were screened for effectiveness in inhibiting mutagenicity of aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P) in the Ames test. Antimutagenicity was evaluated using Salmonella typhimurium strains TA 98 and TA 100. In the assay, metabolic activation of AFB1 (0.5 microg/plate) and B[a]P (1 microg/plate) was mediated by rat liver S9 preparation. Although both plants inhibited mutagenicity, E. officinalis had more inhibitory effect than C. occidentalis. Their action is possibly mediated through interactions with microsomal activating enzymes. Their inhibitory action on chromosomal aberrations together with present results suggest that these plants have potent antimutagenic and anticarcinogenic activities against mutagens requiring metabolic activation.     

Detection of a novel mutagen, 3,6-dinitrobenzo[e]pyrene, as a major contaminant in surface soil in Osaka and Aichi Prefectures, Japan

We previously identified 1,3-, 1,6-, and 1,8-dinitropyrene (DNP) isomers as major mutagens in surface soil in three metropolitan areas of Japan. In the present study, an organic extract from surface soil collected at a park in Takatsuki in Osaka Prefecture, which showed extremely high mutagenicity in Salmonella typhimurium TA98 in the absence of mammalian metabolic system (S9 mix), was investigated to identify major mutagens. A new powerful bacterial mutagen, as well as 1,6- and 1,8-DNP isomers, was isolated from the organic extract (1.8 g) of the soil sample (2.2 kg) by column chromatography. On the basis of mass spectra, the new mutagen, which accounted for 15% of the total mutagenicity of the soil extract, was thought to be a dinitrated polycyclic aromatic hydrocarbon with a molecular weight of m/z 342. The mutagen was synthesized from benzo[e]pyrene by nitration and was determined to be 3,6-dinitrobenzo[e]pyrene (DNBeP) based on its 1H NMR spectrum. The mutagenic potency of 3,6-DNBeP in the Ames/Salmonella assay was extremely high, in that it induced 285,000 revertants/nmol in TA98 and 955,000 revertants/nmol in YG1024 without S9 mix and was comparable to those of DNP isomers, which are some the most potent bacterial mutagens reported so far. In addition to the soil sample from Takatsuki, 3,6-DNBeP was also detected in surface soil samples collected at parks in four different cities, i.e., Izumiotsu and Takaishi in Osaka Prefecture and Nagoya and Hekinan in Aichi Prefecture, and accounted for 22-29% of the total mutagenicity of these soil extracts in TA98 without S9 mix. These results suggest that 3,6-DNBeP is a major mutagen in surface soil and may largely contaminate the surface soil in these two regions in Japan.     

Antimutagenic activities of 24 synthetic flavones with theSalmonella microsomal assay

Twenty-four flavones were synthesized with various hydroxyl and/or methoxyl groups on A and B rings. Their antimutagenic properties were evaluated against benzo(a)pyrene (BaP) and a pool of mutagenic urine concentrate (U) using a modified liquid incubation method of Ames test. The tester strain wasSalmonella typhimurium TA98+S9 Mix. The antimutagenic activities were calculated by non linear regression analysis and the doses of flavones (in nmoles) required for a 50% reduction of induced revertants with BaP and U were defined as the inhibition doses (ID_50B and ID_50U respectively). Seventeen flavones possessed significant antimutagenic activity against BaP. ID_50B ranged from 15.1 nmoles (F22) to 1000.6 nmoles (F13). Eighteen flavones showed significant antimutagenic activity against U. ID_50U ranged from 23.5 nmoles (F22) to 354.6 nmoles (F3). The 2′, 3′, 4′-trihydroxyflavone (F22, ID_50B=15.1 nmoles, ID_50U=23.5 nmoles) and the 2′,3′,4′,7-tetrahydroxyflavone (F20, ID_50B=37.8 nmoles; ID_50U=62.3 nmoles) had antimutagenic activities similar to those of chlorophyllin (ID_50B=19.6 nmoles and ID_50U=44.2 nmoles) and were evaluated against B(a)P 7,8-dihydrodiol-9,10-epoxide. Against this last mutagen, the flavones which included three OH in B ring showed the highest activity and this property seemed independent of the substitutent groups on A ring.     

Genotoxic and antimutagenic activities of extracts from pseudocereals in the Salmonella mutagenicity assay

Extracts of amaranth (Amaranthus L.), sorghum (Sorghumbicolor L.) and Japanese millet (Echinochloafrumentacea L.) were evaluated for mutagenicity in Salmonellatyphimurium strains TA98, TA100 and TA102. All three pseudocereal extracts were also assessed for their antimutagenic properties against the direct mutagens 2-nitrofluorene (2NF) for strain TA98, 3-(5-nitro-2-furyl)acrylic acid (5NFAA) for TA100 and H₂O₂ for TA102 strain and against the indirect mutagen aflatoxin B₁ (AFB₁). No mutagenicity was induced by any of the pseudocereal extracts when tested at concentrations as high as 50 mg/ml. All three extracts showed similar antimutagenicity against 5NFAA and no antimutagenicity against 2NF. The number of revertants induced by H₂O₂ extract was inhibited in order amaranth > Japanese milet > sorghum. All extracts were effective in the inhibition of mutagenic activity of aflatoxin B₁. The total polyphenol content as well as the amount of the flavonoids and phenolic acids as main component of polyphenolics were also determined.     

Effects of riboflavin on benzo(a)pyrene, 2-acetylaminofluorene and methyl methanesulfonate mutagenicity in vitro

Riboflavin was shown to inhibit mutagenicity of benzo(a)pyrene and 2-acetylaminofluorene in the presence of S9 liver fractions deriving from B10.A mice as well as from DBA/2 mice and had no influence on mutagenicity of methyl methanesulfonate. The above findings confirm the supposition that antimutagenicity of riboflavin results from its interaction with enzymes responsible for metabolic activation of promutagens. The antimutagenic effects of riboflavin were more drastic in the presence of liver fractions from B10.A mice than in the presence of those from DBA/2 mice.     

Mutagenic activity of airborne particulate organic pollutants

Organic extracts of airborne particulates collected at eight urban locations and one nonurban site in Southern California were analyzed for mutagenic activity using Ames' Salmonella typhimurium assay system. All urban samples exhibited mutagenic activity, confirming initial findings. The activity was observed with strains susceptible to frameshift mutation and was not enhanced by the addition of a mammalian metabolic activation system, thus suggesting the presence of mutagens other than benzo(a)pyrene and other polycyclic hydrocarbons which require metabolic activation. Assay of 0.1 to 1 mg of the samples resulted in a 5- to 20-fold increase in his⁺ revertants above the background level, with the number of revertants per plate ranging from 0.10 to 0.44 per μg of organic carbon tested.     

Investigation of genotoxic and antigenotoxic activities of Melampodium divaricatum in Salmonella typhimurium.

Melampodium divaricatum is a member of the Asteraceae and in Brazil is known as false-calendula, its flowers being used in anti-inflammatory preparations, substituting the true calendula or marigold (Calendula officinalis L.). The flower extract was investigated for mutagenic and antimutagenic effect in the Salmonella/microsome assay. The tested extract was not mutagenic in the strains TA100, TA98, TA97a and TA102 and decreased the mutagenicity of aflatoxin B1, benzo(a)pyrene and daunomycin. Chlorophyll and triterpenes were detected in the extract, and they might have contributed to the observed effect. Our data suggest that these medicinal plants possess cancer chemopreventive properties.     

Evaluation of the antimutagenic,antigenotoxic, and antioxidant activities of Eriobotrya japonica leaves

Abstract

Context: The leaves of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) are used in traditional medicine to treat inflammatory diseases. However, information about the antigenotoxic and antioxidant properties of its leaves remains to be elucidated.

Objective: The objective of this work was to evaluate the mutagenic/antimutagenic, genotoxic/antigenotoxic, and antioxidant potentials of aqueous and total oligomers flavonoid (TOF) extracts from E. japonica.

Materials and methods: The mutagenic/antimutagenic and genotoxic/antigenotoxic potentials of extracts (50, 250, and 500?µg/plate) were evaluated, respectively, by the Ames test with 48?h incubation and the SOS chromotest test with 2?h incubation. The antioxidant capacity of these extracts (ranging from 50 to 700?µg/mL) was tested using xanthine/xanthine oxidase and the deoxyribose assays.

Results: Eriobotrya japonica extracts showed neither mutagenic nor genotoxic effect. The highest protective effect against methyl methanesulfonate and 2-aminoanthracene was obtained in the presence of aqueous extract, with IC₅₀ values of 80 and 140?µg/plate, respectively, against S. typhimurium TA104. Moreover, this extract (500?µg/plate) was also able to reduce significantly the genotoxicity induced by nitrofurantoin and aflatoxin B1 with IC₅₀ values of 140 and 240?µg/assay, respectively. Likewise, aqueous and TOF extracts inhibited xanthine oxidase and superoxide anion formation with IC₅₀ values ranging from 45 to 95 and from 70 to 90?µg/mL, respectively. However, TOF extract is more efficient in inhibiting hydroxyl radical and chelating iron ion with IC₅₀ values of 140 and 400?µg/mL, respectively, when compared with the aqueous extract.

Conclusion: Eriobotrya japonica prevents the genotoxicity of some carcinogenic substances probably thanks to its antioxidant capacities.     

Mutagencity and antimutagencity studies of lipidic extracts from yellowtail fish (Seriola lalandi), lisa fish (Mugil cephalus) and cazón fish (Mustelus lunulatus).

Organic extracts from fresh and smoked yellowtail fish (Seriola lalandi), lisa fish (Mugil cephalus) and cazon fish (Mustelus lunulatus) were tested for mutagenicity using Ames Salmonella tester strains TA98 and TA100 with metabolic activation (S9). Also, the antimutagenicity of the organic extract from yellowtail fish was tested against aflatoxin B1 (AFB1). Yellowtail fish extract was sequentially fractionated by thin-layer chromatography (TLC) and each fraction was also tested for antimutagenicity. None of the fresh species showed mutagenicity. Extract from smoked yellowtail showed the highest mutagenic potential among the smoked species tested. Organic extract from fresh yellowtail reduced the number of revertants caused by AFB1 showing a dose response type of relationship. Sequential TLC fractionation of the antimutagenic extract produced four antimutagenic fractions from fresh yellowtail fish. These results that the lipidic fraction of the species tested contains at least four compounds with chemoprotective properties that reduce the mutagenicity of AFB1.     

Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants.

This study evaluates the toxic, mutagenic and antimutagenic effects of emerging edible plants that are consumed as new leafy vegetables in Taiwan. Among eight plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of extracts from different parts of the Sol plant, such as leaf and stem, immature fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity with dose dependence and induced significant DNA damage in human lymphocytes based on the comet assay. However, no mutagenicity was found in eight plant extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S. typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However, the potential antimutagenicity of these plant extracts towards B[a]P was weaker than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only the Sol extracts showed strong inhibitory effects in the TA100 system. The antimutagenic activity of water extracts of Sec was partly reduced by heating at 100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be produced in the plant extract preparation process. Fractions with molecular weights above 30,000 showed the strongest antimutagenicity and peroxidase activity in all the fractions of the Sec extracts.     

Antioxidant,mutagenic and antimutagenic activities of an aqueous extract of Limoniastrum guyonianum gall

Abstract

An aqueous extract of Limoniastrum guyonianum gall (G extract) was tested on Salmonella typhimurium to assess its mutagenic and antimutagenic effects. This extract showed no mutagenicity when tested with S. typhimurium strain TA104 either with or without exogenous metabolic activation mixture (S9), whereas our findings revealed that the aqueous gall extract induced a mutagenic effect in S. typhimurium TA1538 when tested in the presence, as well as in the absence, of S9 activation mixture at the concentration of 500?µg/mL. Thus, the same concentration produced a mutagenic effect, when incubated with S. typhimurium TA100 in the presence of metabolic activation mixture. In contrast, our results showed a weak antimutagenic potential of the same extract against sodium azide in the presence of S. typhimurium TA100 and S. typhimurium TA1538 without metabolic activation (S9), whereas, in the presence of S. typhimurium TA104, we obtained a significant inhibition percentage (76.39%) toward 3.25?µg/plate of methylmethanesulfonate. Antimutagenicity against aflatoxin B1, 4-nitro-o-phenylene-diamine and 2-aminoanthracène was significant, with an inhibition percentage of, respectively, 70.63, 99.3 and 63.37% in the presence of, respectively, S. typhimurium TA100, S. typhimurium TA1538 and S. typhimurium TA104 strains at a concentration of 250?µg/plate after metabolic activation (S9). Antioxidant capacity of the tested extract was evaluated using the enzymatic (xanthine/xanthine oxidase assay) and the nonenzymatic (2,2-diphenyl-1-picrylhydrazyl) system. G extract exhibited high antioxidant activity.     

Study on the mutagenicity and antimutagenicity of beta-ionone in the Salmonella/microsome assay.

beta-Ionone (BIO) is a degraded (C(13)) sesquiterpenoid compound found in a variety of edible and aromatic plants. BIO and other ionone derivatives have been used in fragrance products and as flavoring food additives. In this study we investigated the mutagenic and antimutagenic activities of BIO using the Salmonella/microsome assay. Mutagenicity was evaluated by two tests with Salmonella typhimurium strains TA100, TA98, TA97a and TA1535, without and with addition of S9 mixture. A first assay was performed by the plate incorporation procedure and a confirmation test by the pre-incubation method. In either test, no increase in the number of his(+) revertant colonies over the negative (solvent) control values was noted with any of the four tester strains thereby indicating that BIO was not genotoxic in the Salmonella assay. Antimutagenic activity was investigated by testing (by the plate incorporation method) different non-toxic doses of BIO against one or more non-toxic doses of direct-acting (sodium azide: SA, 4-nitroquinoline-N-oxide: 4-NQNO, 2-nitrofluorene: 2-NF and nitro-o-phenylenediamine: NPD) as well as indirect-acting (cyclophosphamide: CP, benzo[a]pyrene: B[a]P, aflatoxin B1: AFB1, 2-aminoanthracene: 2-AA, and 2-aminofluorene: 2-AF) mutagens. BIO did not alter the effects of any direct-acting mutagen or B[a]P and 2-AF. Mutagenic effects of AFB1 and CP, however, were markedly and dose-dependently antagonized by BIO. It has been reported that, in the rat liver, activation of B[a]P and 2-AF depend on CYP1A1 activity, and that CYP2B subfamily is involved in the metabolic activation of CP and AFB1. It has also been described that BIO is a potent inhibitor of CYP2B1/2 and a weaker inhibitor of CYP1A1. Therefore, antagonism of CP-and AFB1-induced mutagenic effects by BIO could have been mediated-at least in part-by the inhibition of CYP2B enzymes.     

DNA binding,adduct characterisation and metabolic activation of aflatoxin B1 catalysed by isolated rat liver parenchymal,Kupffer and endothelial cells

In vitro studies with rat liver parenchymal, Kupffer and endothelial cells isolated from male Sprague-Dawley rats were undertaken to investigate cell-specific bioactivation of aflatoxin B₁, DNA binding and adduct formation. In the mutagenicity studies, using homogenates of all three separated liver cell populations (co-incubated with NADP⁺ and glucose-6-phosphate as cofactors for the cytochrome P-450 monooxygenase system) parenchymal, Kupffer and endothelial cells were able to activate aflatoxin B₁ to a metabolite mutagenic to Salmonella typhimurium TA 98. In the case of nonparenchymal cells (i.e. Kupffer and endothelial cells) 10-fold higher concentrations of aflatoxin B₁ had to be used to obtain a similar number of revertants to that observed with parenchymal cells. Induction studies with Aroclor 1254 led to a striking decrease in the activation of aflatoxin B₁ in parenchymal cells, whereas nonparenchymal cells had a slightly enhanced metabolic activation capacity for aflatoxin B₁. Metabolism studies with microsomes from induced and noninduced cells using testosterone as substrate revealed comparable results: after induction with Aroclor 1254, parenchymal cells showed a 60% decrease in the formation rate of 2-hydroxytestosterone, whereas the formation rate of this metabolite remained unchanged in nonparenchymal cells; 2-hydroxytestosterone is specifically formed by cytochrome P-450 IIC11, which also catalyses the activation of aflatoxin B₁ to its epoxide. When freshly isolated, intact cells were incubated with tritiated aflatoxin B₁, a dose-dependent aflatoxin B₁ binding to DNA in parenchymal and nonparenchymal cells was observed. HPLC analysis of DNA acid hydrolysates of all three cell types showed the major adduct to be 8,9-dihydro-8-(N⁷-guanyl)-9-hydroxyaflatoxin B₁.This project was supported by the Deutsche Forschungsgemeinschaft (SFB 302). B. Schlemper was the recipient of a European Science Foundation Scholarship     

Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro

The current genotoxicity tests of the standard in vitro battery, especially those using mammalian cells, are limited by their low specificity and highlight the importance of new in vitro tools. This study aimed to evaluate the suitability of HepG2 cells for assaying mutagens and promutagens. We determined P53 activity as surrogate genotoxicity endpoint in HepG2 cells. Our results revealed a significant P53-induction by actinomycin D, methyl methanesulfonate and etoposide. Prior to the investigation of promutagens we characterized HepG2 cells by analyzing the expression of 45 genes involved in xenobiotic metabolism and measuring the activity of selected Cytochrome-P450 (CYP) enzymes. We determined a limited metabolic capacity prompting us to employ a co-treatment with rat liver S9 as metabolic activation system (MAS) for promutagens. While cyclophosphamide showed an elevation of activated P53 in the presence of S9, 7,12-dimethylbenz[a]anthracene and aflatoxin B₁ responded without the MAS. Inhibition of cellular CYP3A4 or CYP1A/1B suppressed the aflatoxin B₁- and dimethylbenz[a]anthracene-mediated P53 response, respectively, indicating that HepG2 cells are capable of metabolizing these compounds in a CYP1A/B/3A4-dependent manner. In summary, our results indicate that P53 activation in HepG2 cells combined with a MAS can be used for the identification of new (pro)genotoxicants.     

Mutagenic potential of binary mixtures of nitro-polychlorinated dibenzo-p-dioxins and related compounds

The mutagenic potential of binary mixtures of nitro-polychlorinated dibenzo-p-dioxins and other environmentally related compounds was determined using Salmonella typhimurium strain TA98 in the standard plate incorporation assay. Samples tested included binary mixtures of 4-nitro-4'-chlorobiphenyl with 6-nitro-4,2',3',4',5'-pentachlorobiphenyl, 4-nitrobenzo-p-dioxin with 4-nitro-2,3,8-trichlorodibenzo-p-dioxin, and benzo[a]pyrene with either nitropentachlorobiphenyl or nitrotrichlorodibenzo-p-dioxin. Inhibition was the primary interaction observed for the mixtures of polyhalogenated dioxins or biphenyls with the direct-acting mutagens nitrodibenzo-p-dioxin or nitrochlorobiphenyl. At the highest dose tested, nitrotrichlorodibenzo-p-dioxin inhibited the bacterial mutagenicity of nitrodibenzo-p-dioxin by almost 50%, while pentachlorobiphenyl inhibited the mutagenicity of nitrobiphenyl by 34%. Conversely, synergism was the primary interaction observed for mixtures of halogenated aromatics with the promutagen benzo[a]pyrene. The addition of nitrotrichlorodioxin to benzo[a]pyrene enhanced the mutagenicity of the latter compound by as much as 70%, while the mutagenic potential of a mixture of benzo[a]pyrene and nitropentachlorobiphenyl was approximately 50% greater than the mutagenicity of benzo[a]pyrene alone. In summary, mixtures of nonmutagenic nitropolyhalogenated biphenyls or dibenzo-p-dioxins appear to inhibit the mutagenicity of direct-acting mutagens, while these same compounds seem to enhance the mutagenic potential of the promutagen benzo[a]pyrene.     

Antimutagenic potency of the cytotoxic and anti-psoriatic compound anthralin (cignolin)

The anti-psoriatic compound anthralin (cignolin) was determined to exhibit a strong cytostatic activity on HeLa-K?ln cells; an ED50 concentration of 1.2 microM are cytotoxic for the cells. These growth-inhibition data were confirmed by thymidine-uptake experiments. The drug anthralin was determined to be neither direct a mutagen nor a premutagen in the Ames test using Salmonella typhimurium strain TA 100 (anthralin-concentration = 5 microM). Moreover, this compound was a strong inhibitor of benzo(a)pyrene monooxygenase, an enzyme which causes the metabolic conversion of premutagens to mutagens. These data demonstrate anthralin to be an anti-psoriatic compound devoid of mutagenic property in vitro with regard to base-pair substitutions and provided at least with some antimutagenic potential.     

The antimutagenic activity of Lavandula angustifolia (lavender) essential oil in the bacterial reverse mutation assay.

Essential oils from Melaleuca alternifolia (tea-tree oil) and Lavandula angustifolia (lavender oil) are commonly used to treat minor health problems. Tea-tree oil possesses broad-spectrum antimicrobial activity, and is increasingly used for skin problems. Lavender oil, traditionally used as an antiseptic agent, is now predominantly used as a relaxant, carminative, and sedative in aromatherapy. Despite their growing use no data are available on their mutagenic potential. In this study, after determining the chemical composition of tea-tree oil and lavender oil, by gas-chromatography and mass spectrometry, we investigated their mutagenic and antimutagenic activities by the bacterial reverse mutation assay in Salmonella typhimurium TA98 and TA100 strains and in Escherichia coli WP2 uvrA strain, with and without an extrinsic metabolic activation system. Neither essential oil had mutagenic activity on the two tested Salmonella strains or on E. coli, with or without the metabolic activation system. Conversely, lavender oil exerted strong antimutagenic activity, reducing mutant colonies in the TA98 strain exposed to the direct mutagen 2-nitrofluorene. Antimutagenicity was concentration-dependent: the maximal concentration (0.80 mg/plate) reduced the number of histidine-independent revertant colonies by 66.4%. Lavender oil (0.80 mg/plate) also showed moderate antimutagenicity against the TA98 strain exposed to the direct mutagen 1-nitropyrene. Its antimutagenic property makes lavender oil a promising candidate for new applications in human healthcare.