Toxicological Assessment of Intermediates in Natural Attenuation of p-Xylene to Marine Microalgae.

The toxic effects of p-xylene, 4-methylbenzyl alcohol, p-methyl benzaldehyde, and p-toluic acid on two marine microalgae (Phaeodactylum tricornutum Bohlin, and Skeletonema costatum) were investigated. p-Xylene was the most toxic to Pha. tricornutum with a 96 h EC50 value of 6.76 mg L-1. Based on the 96 h EC50 values for two microalgae, the toxicity of the four chemicals, in descending order, was: p-xylene, p-methyl benzaldehyde, 4-methylbenzyl alcohol, then p-toluic acid. The results showed that the toxicity of the transformed products of p-xylene was lower than that of p-xylene.

Acute and 28-day sub-acute intravenous toxicity studies of 1'-S-1'-acetoxychavicol acetate in rats.

1'-S-1'-acetoxychavicol acetate (ACA) has been previously reported to reduce tumor volume in nude mice, at an effective dose of 1.56 mg/kg body weight. However, the detailed toxicological profile for ACA has not yet been performed. Herein, we investigated the toxicity of intravenous administration of ACA in male and female Sprague-Dawley rats, both acutely (with single doses of 2.00, 4.00 and 6.66 mg/kg body weight, for 14 days), and sub-acutely (with weekly injections of 0.66, 1.33, and 2.22 mg/kg, for 28 days). In both toxicity studies, treatment with ACA did not affect behavior, food/water intake or body weight, nor did it induce any changes in clinically relevant hematological and biochemical parameters or mortality, suggesting that the LD50 of ACA was higher than 6.66 mg/kg body weight, regardless of sex. Sub-acutely, there was however, mild focal inflammation of kidneys and lobular hepatitis, but these were not associated with significant functional adverse effects. Therefore, the no-observed-adverse-effect level (NOAEL) for intravenous administration of ACA in the present 28-day sub-acute study was 2.22 mg/kg body weight, in both male and female rats. These findings provide useful information regarding the safety of ACA use in a healthy, non-tumor-bearing rat model.

Discovery of (2-aminophenyl)methanol as a new molecular chaperone that rescues the localization of P123S mutant pendrin stably expressed in HEK293 cells.

Pendred syndrome is the most common form of syndromic deafness. It is associated with a mutation in the SLC26A4 gene that encodes pendrin, which is thought to maintain the ion concentration of endolymph in the inner ear most likely by acting as a chloride/bicarbonate transporter. Mutations in the SLC26A4 gene are responsible for sensorineural hearing loss. In this study, we established a stable HEK293 cell line expressing P123S mutant pendrin and developed screening methods for compounds that show pharmacological chaperone activity by image analysis using CellInsight™. Morphological analysis of stained cells in each well of 96-well plates yielded six compounds in the compound library. Furthermore, fluorescence intensity analysis of the intracellular localization of P123S mutant pendrin in HEK293 cells using FLUOVIEW™ and cytotoxicity experiments revealed that (2-aminophenyl)methanol 8 is the most promising molecular chaperone to rescue P123S mutant pendrin: the plasma membrane (M)/cytoplasm (C) ratios are 1.5 and 0.9 at the concentrations of 0.3 and 0.1mM, respectively, and a sustained effect was observed 12h after removal of the compound from the cell medium. Because the M/C ratio of salicylate, which was previously discovered as a molecular chaperone of P123S mutant pendrin, was approximately 1 at 10mM concentration and a sustained effect was not observed even at 6h, (2-aminophenyl)methanol 8 was 100 times more potent and exhibited a longer sustained effect than salicylate. These findings suggest that (2-aminophenyl)methanol 8 is an attractive candidate for therapeutic agent for Pendred syndrome patients.

Toxicological effects of a mixture used in weight loss products: p-synephrine associated with ephedrine, salicin, and caffeine.

p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has been used for weight loss in dietary supplements. There are commercial products containing this substance associated to caffeine, salicin, and ephedrine. The aim of this study was to evaluate the acute toxicity of this mixture in mice of both sexes. The significative results observed after acute oral administration to male and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine, salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor activity and ptosis in all treated groups for both sexes. Seizures were also observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400 mg/kg), and piloerection (all treated groups) were significantly observed only in females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was confirmed through the spontaneous locomotor activity test, in which the number of crossings considerably decreased (P < .01) in all treated groups. The rotarod test showed a decrease in motor coordination at 400 mg/kg. Body temperature decreased significantly (P < .01) in all treated groups compared to controls. The results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin, and caffeine association; this toxicity augments the attentiveness on commercial products containing this mixture, given the expressive number of adverse events related to its utilization.

Predicting mixture toxicity of seven phenolic compounds with similar and dissimilar action mechanisms to Vibrio qinghaiensis sp.nov.Q67.

The predictions of mixture toxicity for chemicals are commonly based on two models: concentration addition (CA) and independent action (IA). Whether the CA and IA can predict mixture toxicity of phenolic compounds with similar and dissimilar action mechanisms was studied. The mixture toxicity was predicted on the basis of the concentration-response data of individual compounds. Test mixtures at different concentration ratios and concentration levels were designed using two methods. The results showed that the Weibull function fit well with the concentration-response data of all the components and their mixtures, with all relative coefficients (Rs) greater than 0.99 and root mean squared errors (RMSEs) less than 0.04. The predicted values from CA and IA models conformed to observed values of the mixtures. Therefore, it can be concluded that both CA and IA can predict reliable results for the mixture toxicity of the phenolic compounds with similar and dissimilar action mechanisms.

Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

[Experimental studies on toxic effects of Tiangou Jiangya capsule].

OBJECTIVE: To study the acute and chronic toxicity of Tiangou Jiangya capsule. METHOD: Tiangou Jiangya capsule was intragastrically administered to mice twice a day. The appearance, behavior, mental status, respiratory changes of mice and the number of poisoned and dead mice in each group were noted daily for 14 consecutive days. The amount of weight and feed of survived mice were recorded every day. The mice were divided into four groups: the treatment groups (minimum, middle, maximum dose of Tiangou Jiangya capsule) and the control group. After continuously orally administrated for 6 months, the rats' behavior, weight gain, food consumption, indications for hematology, blood biochemistry, urine analysis, electrocardiogram, systematic autopsy and histopathology were observed. The above physiological indexes were inspected again 1 month after cease of administration. RESULT: The oral acute toxicity study of Tiangou Jiangya capsule in mice revealed that the maximum dose is 534.86 g x kg(-1), which was 534.86 times the recommended human maximum dose in clinical practice. Compared with normal control group, no significant differences were observed in rats' behaviors, food-intake, electrocardiogram and relative examination indexes among the treatment groups. There was no difference of hematology, biochemistry test, urine and histopathology. CONCLUSION: The minimum dosage of Tiangou Jiangya capsule is relatively safe. It caused weight loss by administrated with the middle and maximum dose for 6 months, which should be paid attention in clinical studies.

Gastrodin attenuates perfluorooctanoic acid-induced liver injury by regulating gut microbiota composition in mice.

Perfluorooctanoic acid (PFOA) can accumulate in the livers of humans and animals via the food chain, resulting into liver injury, which is closely related to intestinal flora dysbiosis. Gastrodin has been reported to have hepatoprotective effect. However, whether gastrodin can alleviate PFOA-induced liver injury via modulating gut microbiota remains unclear. Herein, a PFOA-induced liver injury model was established by gavage of PFOA (5 mg/kg body weight) in 2% Tween 80 solution once daily for 6 weeks in mice, and then gastrodin in saline (20 mg/kg body weight) was used once daily for 8 weeks to treat liver damage. The biochemical indexes associated with liver function, oxidative stress, and inflammatory factors were examined. Hematoxylin-eosin staining was used to determine the liver histopathological changes. Besides, 16S rRNA sequencing was used to analyze the difference of gut microbiota between the model and treatment groups. The results showed that gastrodin significantly improved the oxidative stress caused by PFOA. Intestinal flora analysis showed that gastrodin treatment significantly increased the relative abundance of probiotics, such as Lactobacillus, Bifidobacterium, and Bacteroides, while the harmful bacteria, including Desulfovibrio were decreased. Gastrodin treatment also significantly increased the level of short-chain fatty acids (SCFAs), such as butyric acid and isobutyric acid. Spearman correlation analysis showed that the composition changes of gut microbiota and SCFAs increase were both beneficial to alleviate the liver injury caused by PFOA. To sum up, gastrodin can effectively alleviate PFOA-induced liver injury through regulating gut microbiota composition.

RIFM fragrance ingredient safety assessment, p-isopropylbenzyl alcohol, CAS Registry Number 536-60-7.

The existing information supports the use of this material as described in this safety assessment. p-Isopropylbenzyl alcohol was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from the read-across analog benzyl alcohol (CAS # 100-51-6) show that p-isopropylbenzyl alcohol is not expected to be genotoxic. Data from the read-across analog benzyl alcohol (CAS # 100-51-6) provide a calculated MOE >100 for the repeated dose, developmental, and local respiratory toxicity endpoints. The reproductive toxicity endpoint was evaluated using the TTC for a Cramer Class I material, and the exposure is below the TTC (0.03 mg/kg/day). Data from read-across analog benzyl alcohol (CAS # 100-51-6) provided p-isopropylbenzyl alcohol a NESIL of 5900 µg/cm2 for the skin sensitization endpoint. The phototoxicity and photoallergenicity endpoints were evaluated based on UV spectra; p-isopropylbenzyl alcohol is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; p-isopropylbenzyl alcohol was found not to be a PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC) are <1.

Enzymatic decolorization of melanin by lignin peroxidase from Phanerochaete chrysosporium.

Skin darkening results as a consequence of the accumulation of skin pigment melanin. To combat this, the amplitude of skin lightening agents are commercially available, most of which inhibit melanin synthesis. Decolorization of melanin is an alternative method of skin lightening. In this study, we show that lignin peroxidase (LiP), an extracellular enzyme purified from Phanerochaete chrysosporium NK-1 isolated from a forest soil can effectively degrade and decolorize melanin in vitro. Decolorization conditions including pH, temperature, incubation time, enzyme concentration, and mediator addition were investigated to optimize the reaction conditions. The results indicate that pH 3, 40 °C, 15 IU/ml, and 10 h incubation were the optimal conditions for the decolorization of the melanin. The use of the mediator, veratryl alcohol was also found effective to enhance the efficacy of the melanin decolonization, with up to 92% decolorization. The scanning electron microscopy results showed void spaces on the treated melanin granules as compared to the untreated sample, indicating the degradation of melanin. Changes in the fingerprint region of the melanin were observed. Between wavenumbers 1500-500 cm-1, for example, the presence of new peaks in the treated melanin at 1513, 1464, and 1139 cm-1 CH2, CH3 bend and C-O-C stretch represented structural changes. A new peak at 2144 cm-1 (alkynyl C≡C stretch) was also detected in the decolorized melanin. The cytotoxicity study has shown that the treated melanin and LiP have low cytotoxic effects; however, the mediator of veratryl alcohol could result in high mortality which suggests that its use should be meticulously tested in formulating health and skincare products. The findings of the study suggest that LiP produced by Phanerochaete chrysosporium has the potential to be used in the medical and cosmetic industries, particularly for the development of biobased cosmetic whitening agents.

Tissue-Adhesive Paint of Silk Microparticles for Articular Surface Cartilage Regeneration.

Current biomaterials and tissue engineering techniques have shown a promising efficacy on full-thickness articular cartilage defect repair in clinical practice. However, due to the difficulty of implanting biomaterials or tissue engineering constructs into a partial-thickness cartilage defect, it remains a challenge to provide a satisfactory cure in joint surface regeneration in the early and middle stages of osteoarthritis. In this study, we focused on a ready-to-use tissue-adhesive joint surface paint (JS-Paint) capable of promoting and enhancing articular surface cartilage regeneration. The JS-Paint is mainly composed of N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide (NB)-coated silk fibroin microparticles and possess optimal cell adhesion, migration, and proliferation properties. NB-modified silk fibroin microparticles can directly adhere to the cartilage and form a smooth layer on the surface via the photogenerated aldehyde group of NB reacting with the -NH2 groups of the cartilage tissue. JS-Paint treatment showed a significant promotion of cartilage regeneration and restored the smooth joint surface at 6 weeks postsurgery in a rabbit model of a partial-thickness cartilage defect. These findings revealed that silk fibroin can be utilized to bring about a tissue-adhesive paint. Thus, the JS-Paint strategy has some great potential to enhance joint surface regeneration and revolutionize future therapeutics of early and middle stages of osteoarthritis joint ailments.

1'-Acetoxychavicol acetate-induced cytotoxicity is accompanied by a rapid and drastic modulation of glutathione metabolism.

The effect of 1'-acetoxychavicol acetate (ACA), an anticarcinogenic compound naturally obtained from rhizomes and seeds of South East Asia plants, on the intracellular concentration of glutathione and the activities of enzymes related to glutathione metabolism was studied in Ehrlich ascites tumor cells. We showed in a previous study that ACA induced apoptosis in tumor cells and the cell death was reversed by the addition of N-acetlycysteine or glutathione ethylester. Here we found that ACA caused a rapid decrease in glutathione level in less than 10 min after ACA exposure. At the time, glutathione reductase activity was significantly inhibited and gamma-glutamyl cysteine increased by ACA exposure. These results show that ACA caused the decrease in the intracellular GSH levels in Ehrlich ascites tumor cells, suggesting that ACA-induced decrease of the cellular GSH levels can lead to growth arrest of cancer and enhancement of the efficacy other anticancer drugs.

Antibodies to neural proteins in organophosphorus-induced delayed neuropathy (OPIDN) and its amelioration.

The development of OPIDN and the efficacy of experimental intervention using the calcium-channel blocker verapamil were used as a model to test the serial time-measurements of serum autoantibodies against neuronal cytoskeletal proteins [e.g., neurofilament triplet (NF)] and glial proteins [myelin-basic protein (MBP) and glial fibrillary-acidic protein (GFAP)] as biomarkers of neurotoxicity and its amelioration. Ten White Leghorn hens (>7 months, 1.2-1.8 kg) were administered phenyl-saligenin phosphate (PSP; 2.5 mg/kg; im), a dose reported to induce a 70% decrease in neurotoxic esterase (NTE) activity. Five of the hens were administered verapamil (7 mg/kg; im) for 4 days starting one day before PSP administration. Serum was isolated from blood collected by serial brachial venepuncture before PSP (day 0) administration and on days 3, 7 and 21 after PSP administration, each hen acting as its own control. Serum antibodies (IgG) to NF-L, NF-M, NF-H, MBP, and GFAP were assayed using an ELISA. There were no detectable levels of antibodies on days 0 and 3. IgG against all neural proteins were detected on days 7 and 21, with titer levels being significantly (p< or =0.05) higher in sera of hens receiving PSP only. Anti-NF-L titers were highest compared to those against NF-M, NF-H or MBP at 21 days. Titers of anti-NF-L and anti-MBP significantly (p< or =0.01) correlated with clinical scores at days 7 and 21. Detection of anti-NF and anti-MBP antibodies confirms the neuroaxonal degeneration accompanied by myelin loss reported in this model of OPIDN and the amelioration of neuropathy using verapamil. The detection of anti-GFAP antibodies suggests CNS involvement in OPIDN, since astrocytes are only found therein. This study demonstrates that detection of neuroantibodies can be used as biomarkers of neuropathy development and to monitor the amelioration resulting from therapeutic intervention. Together with biomarkers of exposure neuroantibodies can be used to monitor neuropathogenesis due to environmental or occupational exposures.

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities.

2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/micromol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were approximately 1-3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects ( approximately 50-400 revertants/micromol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at >or=1.9 microM). 4-A-2,6-DNBA was positive at 432 microM; the weakest effect was observed with 2,4,-DNBA (positive at >or=920 microM). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man.

Use of genetically manipulated Salmonella typhimurium strains to evaluate the role of human sulfotransferases in the bioactivation of nitro- and aminotoluenes.

Various nitro- and aminotoluenes demonstrated carcinogenic activity in rodent studies, but were inactive or weakly active in conventional in vitro mutagenicity assays. Standard in vitro tests do not take into account activation by certain classes of enzymes. This is true in particular for sulfotransferases (SULTs). These enzymes may convert aromatic hydroxylamines and benzylic alcohols, two major classes of phase-I metabolites of nitro- and aminotoluenes, to reactive esters. Here it is shown that expression of certain human SULTs in Salmonella typhimurium TA1538 or TA100 strongly enhanced the mutagenicity of various nitrotoluenes and nitro- and amino-substituted benzyl alcohols. Human SULT1A1, SULT1A2, and SULT1C2 showed the strongest activation. The observation that some nitrotoluenes as well as some aminobenzyl alcohols were activated by SULTs in the absence of cytochromes P450 implies that mutagenic sulfuric esters were formed at both the exocyclic nitrogen and the benzylic carbon, respectively. Nitroreductase deficiency (using strain YG7131 instead of TA1538 for SULT1A1 expression) did not affect the SULT-dependent mutagenicity of 1-hydroxymethylpyrene (containing no nitro group), moderately enhanced that of 2-amino-4-nitrobenzyl alcohol, and drastically attenuated the effects of nitrobenzyl alcohols without other substituents. The last finding suggests that either activation occurred at the hydroxylamino group formed by nitroreductase or the nitro group (having a strong -M effect) had to be reduced to an electron-donating substituent to enhance the reactivity of the benzylic sulfuric esters. The results pointed to an important role of SULTs in the genotoxicity of nitrotoluenes and alkylated anilines. Activation occurs at nitrogen functions as well as benzylic positions.

Analysis of the leaching and toxicity of new amine activators for the curing of acrylic bone cements and composites.

The comparative reactivity of new tertiary amine activators with the basic chemical structure of N,N-dimethyl-4-toluidine, but reduced toxicity, is analysed. The leaching of the amine compounds from cured cements was studied by analysis of the concentration of the corresponding amine in a physiological saline solution after 3 months of immersion, giving lower values for the new amine compounds as compared to N,N-dimethyl-4-toluidine. The acute toxicity was determined by intravenous injection of saline solutions of the corresponding chlorhydrates in mice and the cytotoxicity by the evolution of specific culture media. The results obtained demonstrate a lower acute toxicity and cytotoxicity of the new activators, even with a noticeable antiseptic action, which makes these materials very interesting from a practical point of view as activators of the curing process of acrylic bone cements for orthopaedic surgery and dentistry.

Activation of benzylic alcohols to mutagens by rat and human sulfotransferases expressed in Escherichia coli.

Human hydroxysteroid sulfotransferase, human phenol-sulfating form of phenol sulfotransferase, rat hydroxysteroid sulfotransferase a and rat phenol sulfotransferase IV were expressed in Escherichia coli. Cytosol preparations of transformed bacteria were used as activating systems in mutagenicity tests with Salmonella typhimurium TA98. All test compounds, 1-hydroxymethylpyrene, 2-hydroxymethylpyrene, 1-(1-pyrenyl)ethanol, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 4H-cyclopenta[def]chrysen-4-ol, were activated by both hydroxysteroid sulfotransferases investigated. However, 1-(1-pyrenyl)ethanol was 67-fold more efficiently activated by the human enzyme, whereas 7-hydroxymethyl-12-methylbenz[a]anthracene was 27-fold more efficiently activated by the rat enzyme. The phenol sulfotransferases showed relatively low activities with the benzylic alcohols investigated. The only exception was 4H-cyclopenta[def]chrysen-4-ol, which was activated efficiently by rat phenol sulfotransferase IV. We had previously tested the ability of rat and human hepatic cytosol preparations to activate the same compounds. The results of a statistical analysis suggest that the activities of human hydroxysteroid sulfotransferase, rat hydroxysteroid sulfotransferase a and phenol sulfotransferase IV can account for a substantial portion of the activation of benzylic alcohols in human, female rat and male rat liver, respectively.

Expression of human estrogen sulfotransferase in Salmonella typhimurium: differences between hHST and hEST in the enantioselective activation of 1-hydroxyethylpyrene to a mutagen.

Various human sulfotransferases (hP-PST, hM-PST, hHST) and rat sulfotransferases (rPST-IV, rHSTa) have already been expressed in Ames' Salmonella strains (in particular in TA1538). Now a further strain, TA1538-hEST, which expresses the human estrogen sulfotransferase (hEST), has been constructed. This strain activated the primary benzylic alcohol 1-hydroxymethylpyrene (1-HMP) and the secondary benzylic alcohol 1-hydroxyethylpyrene (1-HEP) to mutagens. Human sulfotransferases hEST and hHST both activated 1-HEP, but they differed substantially in their enantioselectivity for this compound.