Biomedical subjects

M Blanco

Publications and source records attributed to M Blanco.

At least 73 records · Page 4Linked to original sources

PubMed2000

Mutagenicity of 80 chemicals in Escherichia coli tester strains IC203, deficient in OxyR, and its oxyR(+) parent WP2 uvrA/pKM101: detection of 31 oxidative mutagens.

Strain IC203, deficient in OxyR, and its oxyR(+) parent WP2 uvrA/pKM101 (denoted IC188) are the basis of a new bacterial reversion assay, the WP2 Mutoxitest, which has been used in the evaluation of 80 chemicals for oxidative mutagenicity. The following 31 oxidative mutagens were recognized by their greater mutagenic response in IC203 than in IC188: (1) peroxides: hydrogen peroxide (HP), t-butyl hydroperoxide (BOOH) and cumene hydroperoxide (COOH); (2) benzoquinones (BQ): 2-methyl-1,4-BQ, 2,6-dimethyl-1,4-BQ and 2,3, 5,6-tetramethyl-1,4-BQ; (3) naphthoquinones (NQ): 1,4-NQ, 2-methyl-1, 4-NQ and 2-hydroxy-1,4-NQ; (4) phenol derivatives: catechol, hydroquinone, pyrogallol, 1,2,4-benzenetriol, t-butylhydroquinone, gallic acid and 4-aminophenol; (5) catecholamines: DL- and L-dopa, DL- and L-epinephrine, dopamine and L-norepinephrine; (6) thiols: L-cysteine methyl ester, L-cysteine ethyl ester, L-penicillamine and dithiothreitol; (7) diverse: 3,4-dihydroxyphenylacetic acid, hypoxanthine and xanthine, both in the presence of xanthine oxidase, L-ascorbic acid plus copper (II) and phenazine methosulfate. Among these oxidative mutagens, 25 were found to be uniquely positive in IC203. With the exception of BOOH and COOH, mutagenesis by all oxidative mutagens was inhibited by catalase present in rat liver S9, indicating that it is mediated by HP generation, probably in autoxidation reactions. These catalase-sensitive oxidative mutagens were poor inducers of mutations derived from 8-oxoguanine lesions, whereas such mutations were efficiently induced by organic hydroperoxides. The results support the usefulness of incorporating IC203 in the bacterial battery for testing of chemicals. The well-characterized oxidative mutagens available with the use of the WP2 Mutoxitest may serve as a reference in studies on the genotoxicity of oxidative stress.

Animals↗

PubMed2000

Toxigenic Escherichia coli isolated from pigs in Argentina.

The presence of porcine toxigenic E. coli (ETEC, VTEC) in 28 piggeries (5% of total) of the central and northeast region of Argentina was studied for a better understanding of the epidemiology of porcine strains. Samples were taken by rectal swabs from healthy piglets and from those with diarrhoea, in addition to their dams. Between 5-10 colonies were isolated from each one of 223 animals sampled from 1992 to 1997. By using specific primers each strain was screened by PCR for VT1, VT2all, VT2e, STIa, and LTI toxin genes. Only strains positive for any of the toxins mentioned above were screened for STb. Their O serogroups were determined by agglutination. All of the above enterotoxins and verocytotoxins were found in E. coli isolated from the animals. The STIa gene was detected in E. coli isolated from 27/127 piglets with diarrhoea, in comparison with LTI (4/127 pigs). No toxin gene was amplified from E. coli isolated from either healthy piglets or their dams. When strains isolated from 48 piglets without diarrhoea but showing delayed growth were analysed by PCR, their toxin profile was determined to be VT1 (1/48 piglets), VT2all (5/48), STIa (1/48), LTI (3/48) and VT2e (3/48). Serogroup O64 prevailed among ETEC; O138 prevailed for ETEC/VTEC strains. This is the first extensive study regarding porcine toxigenic E. coli in Argentina and constitutes an important database for the implementation of prevention measures.

Agglutination Tests↗

PubMed2000

Efficacy and safety of valsartan compared with enalapril at different altitudes.

OBJECTIVE: To compare the safety, tolerability, and antihypertensive efficacy of valsartan with enalapril at different altitudes. METHOD: A total of 142 adult Colombian outpatients with mild to moderate essential hypertension were recruited in 3 cities at different altitudes (Bogotá at 2600 m, Medellin at 1538 m and Barranquilla at 100 m) and randomized in an open label fashion to receive either valsartan 80 mg once daily or enalapril 20 mg once daily for 8 weeks. Those patients not responding at 4 weeks received additional 1.25 mg indapamide daily during the remaining trial period. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to 4 weeks. Secondary efficacy variables included the change in mean sitting systolic blood pressure (SSBP). The primary criterion for tolerability was the incidence of adverse experiences. RESULTS: Both valsartan and enalapril reduced mean SDBP and SSBP with similar efficacy, independent of altitude. Adverse events irrespective of relationship to trial drug were reported by 12 patients (18.8%) on valsartan and by 15 (23.4%) patients on enalapril. Enalapril was associated with a significantly (P<0.05) higher rate of dry cough and more cases of headache than valsartan. CONCLUSIONS: Valsartan 80 mg once daily is as effective as enalapril 20 mg once daily in reducing blood pressure, with tolerability profile at least as good as enalapril's.

Adult↗

PubMed2000

Forensic identification of skeletal remains from members of Ernesto Che Guevara's guerrillas in Bolivia based on DNA typing.

We report the positive identification of several members of the guerrillas led by Ernesto "Che" Guevara on the 1960 s in Bolivia by means of DNA fingerprinting. Successful DNA typing of both short tandem repeat loci and the hypervariable region of the human mitochondrial DNA was achieved after extracting total DNA from bones obtained from two burial sites. Given the size of the Cuban database for the STR allele frequencies, a conservative approach was followed to estimate the statistical significance of the genetic evidence. The estimated probabilities of paternity for the two cases in which the paternity logic was applied were higher than 99%. One case was analyzed using mitochondrial DNA and could not be excluded from the identity proposed by the forensic anthropology team. A fourth case was identified by exclusion, on the basis of the positive identification of the other remains, the historical and other anthropological evidence.

Alleles↗

PubMed2000

Development and validation of a near infrared method for the analytical control of a pharmaceutical preparation in three steps of the manufacturing process.

A near infrared diffuse reflectance spectroscopy (NIRS) procedure for the quantitative control analysis of the active compound (otilonium bromide) in a pharmaceutical preparation in three steps of the production process (blended product, cores and coated tablets) and a methodology for its validation are proposed. The analytical procedure is composed by two consecutive steps. First, the sample is identified by comparing its spectrum with a second derivative spectral library. If the sample is positively identified, the active compound is quantified by using a previously established partial least squares (PLS) calibration model. The procedure was validated by studying repeatability, intermediate precision, accuracy and linearity. To this end, an adaptation of ICH (International Conference on Harmonisation) validation methodology to an NIR multivariate calibration procedure is proposed. The relative standard error of prediction (RSEP) was < or = 1% and the suitability of the procedure for control analysis was confirmed by the results obtained analysing new production samples produced over a three-month period.

Calcium Channel Blockers↗

PubMed2000

[Effect of Helicobacter pylori eradication on histological lesions of gastric mucosa. An 18-month follow-up study].

OBJECTIVE: To evaluate the effect of Helicobacter pylori eradication on pathologic lesions over the gastric mucosa during an 18-month follow-up period. PATIENTS AND METHODS: A total of 122 duodenal ulcer patients infected with H. pylori were prospectively studied. Patients were randomized to receive: ranitidine alone, ranitidine plus antibiotics, or bismuth plus antibiotics. An endoscopy was performed at 3, 6, 12 and 18 months. Haematoxylin-eosin, Giemsa, and Warthin-Starry staining methods were used. Histologic lesions were classified according to the following score: normal (0); superficial chronic gastritis (CG): mild (0.5), moderate (1) and severe (1.5); atrophic CG: mild (2), moderate (3) and severe (4); intestinal metaplasia: absence (0), mild (1), moderate (2) and severe (3). The acute inflammatory activity (active CG) was scored from 0 to 3 (absence, mild, moderate, severe) regarding: inflammatory density in the lamina propria, density of plymorphonuclear leukocytes in the lamina propria, density of intra-epithelial polymorphonuclear leukocytes and superficial erosions. RESULTS: H. pylori eradication was achieved in 31% of patients (0% in the group of ranitidine alone and 48% in patients who received antibiotics). The score corresponding to CG declined progressively after H. pylori eradication, with average values of 2.1 +/- 1.3, 1.98 +/- 1.4, 1.73 +/- 1.6, 1.43 +/- 1.9 and 1.38 +/- 1.9 (p < 0.0001) at 0, 3, 6, 12 and 18 months, respectively. The corresponding score for active CG also improved progressively after eradication: 7.82 +/- 1, 2.51 +/- 0.7, 1.24 +/- 0.6, 0.45 +/- 1.6 and 0.12 +/- 0.5 (p < 0.0001). Nevertheless, no changes were observed regarding atrophia or intestinal metaplasia conditions. CONCLUSIONS: H. pylori eradication is associated with a histologic improvement of gastric mucosa. It begins early and continues for the 18 months after therapy. The improvement in the overall inflammatory component is slow and progressive. In contrast, improvement of the acute component in gastritis is more marked early, and is observed immediately after eradication. Nevertheless, H. pylori eradication is not followed by an improvement in atrophy or intestinal metaplasia.

Adolescent↗

PubMed2000

Identification and quantitation assays for intact tablets of two related pharmaceutical preparations by reflectance near-infrared spectroscopy: validation of the procedure.

Quantitative analysis based on near-infrared (NIR) spectroscopy uses individual calibration equations for each sample studied because of the need to model all possible chemical and physical variability sources. A NIR method, using a fibre optical probe, for the analysis of two different and related pharmaceuticals from two different production steps (cores and tablets) is studied. Both pharmaceuticals have the same active principle and similar excipients, but with different nominal concentration values. The pharmaceuticals are identified by comparison using a second-derivative spectral library; an identification procedure consisting of two-steps (cascade) library: correlation coefficient followed by maximum distance in wavelength space is proposed. Once a sample has been positively identified, the active principle is quantified with partial least-squares regression (PLSR) using a sole and global calibration. The proposed method was validated for use as a control method, and for this purpose selectivity of the identification process, and the repeatability, intermediate precision, accuracy, linearity, and robustness of the active principle quantitation, were assessed.

Algorithms↗

PubMed2000

Phorboid 20-homovanillates induce apoptosis through a VR1-independent mechanism.

BACKGROUND: Vanilloids, such as capsaicin and resiniferatoxin (RTX), are recognized at the cell surface by vanilloid receptor type 1 (VR1), which has recently been cloned. VR1 mediates the effects of capsaicin and RTX in VR1-expressing cells, but vanilloids can induce apoptosis through a pathway not mediated by VR1. Phorboid 20-homovanillates can be used to investigate cell death induced by vanilloids. RESULTS: 12,13-Diacylphorbol-20 homovanillates were prepared by the sequential esterification of the natural polyol. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV) induced apoptosis in Jurkat cells to the same extent as RTX. Apoptosis was preceded by an increase in intracellular reactive oxygen species and by the loss of mitochondrial transmembrane potential. PPAHV-induced apoptosis was mediated by a pathway involving caspase-3 activation and was initiated at the S phase of the cell cycle. The cell-death pathway triggered by VR1 activation was studied in 293T cells transfected with the cloned rat vanilloid receptor. In this system, capsaicin and PPAHV induced cell death by an apparent necrotic mechanism, which was selectively inhibited by the competitive vanilloid receptor antagonist capsazepine. Interestingly, phorbol-12, 13-bisnonanoate-20-homovanillate, an analogue of PPAHV, induced cell death in VR1-transfected cells but could not trigger apoptosis in the Jurkat cell line. CONCLUSIONS: Vanilloids can induce cell death through different signalling pathways. The cell death induced in a VR1-independent manner has the hallmark of apoptosis, whereas the cell death mediated by vanilloids binding to VR1 is seemingly necrotic. Phorboid homovanillates that have antitumour and anti-inflammatory activities but lack the undesirable side effects of the natural vanilloids could be developed as potential drugs.

Apoptosis↗

PubMed2000

Virulence genotypes and serotypes of verotoxigenic Escherichia coli isolated from cattle and foods in Argentina. Importance in public health.

Virulence factors of Verotoxin-producing Escherichia coli (VTEC) strains isolated from hamburgers and ground beef were studied in Argentina by PCR. Their virulence profiles were correlated with those corresponding to strains isolated from calves and adult cattle. Most virulent profiles (VTs+ eae+ Mp+) were present in E. coli from healthy and diarrheic calves corresponding to O5:H-, O5:H27, O20:H?, O26:H11, O38:H?, O103:H-, O103:H2, O111:H-, O118:H16, O165:H-serotypes. The presence of the eae gene was significantly more frequent among VTEC strains isolated from calves (20/26; 76%) than from adult cattle (1/39; 2.5%) (p < 0.005). VT2+ eae- E. coli was prevalent in foods and adult cattle at slaughterhouse. The prevalence of the eae gene was similar between VTEC strains isolated from meat (0/21) and adult cattle (1/39; 2.5%) which constitutes the main population processed at slaughterhouses in Argentina. Serotyping showed that VTEC strains were distributed among 31 serotypes, some of which (O20:H19, O91:H21, O113:H21, O116:H21, O117:H7, O171:H2, OX3:H21) were shared between bovine and food strains. These O serogroups have been isolated from cases of haemorrhagic colitis (HC) and haemolyticuraemic syndrome (HUS) in humans in several continental European countries. This study confirms the role of cattle as a reservoir of many VTEC serotypes other than O157:H7 and represents a base for future diagnostic, prevention and control strategies of EHEC in this country. In addition, this study affirms the advantages of PCR-based screening of E. coli isolates given the finding of so many verotoxin-producing strains.

Adhesins, Bacterial↗

PubMed2000

Polymorphic analysis of a pharmaceutical preparation by NIR spectroscopy.

A method for the characterization and determination of the crystalline from present in the amorphous miokamycin of a pharmaceutical preparation using near-infrared spectroscopy (NIRS) is proposed. The study leading to the development of the proposed method involved both qualitative (classification by residual variance analysis) and quantitative aspects (the determination of both total miokamycin and its crystalline form using multivariate calibration). Samples containing less than 5% of the total amount of miokamycin in its crystalline form can be accurately classified. Partial least-squares regression (PLSR) allows low contents of the crystalline form to be determined with absolute errors less than 1.5%, which is comparable to the limit of detection of the X-ray diffraction technique used as reference. Also, the total miokamycin content is determined by NIRS with errors less than 1%. The simplicity, expeditiousness and robustness of the proposed method make it an effective tool for determining both total and crystalline miokamycin in solid dosage forms.

Least-Squares Analysis↗

PubMed2000

Value of quantitative serology for confirmation of Helicobacter pylori eradication: an 18-month follow-up study.

In this study several therapies were administered to 124 H. pylori-positive patients and IgG antibody titers were measured by ELISA at months 0, 2, 3, 6, 12, and 18 months. Serum titers of IgG antibody progressively decreased after H. pylori eradication; at 3 months, the area under the receiver operating characteristic curve for the decrease of IgG antibody titers for confirming H. pylori eradication was 0.99, with 100% sensitivity and 99% specificity (when the cutoff point was set at 3 U/mL). We conclude that a decrease in serum titers of IgG antibody to H. pylori relatively early after completion of therapy (1 month after ranitidine or bismuth therapy is completed and 2.5 months after antibiotic therapy is completed) can be used as a noninvasive, simple, and inexpensive method to confirm H. pylori eradication.

Adult↗

PubMed2000

Helicobacter pylori infection, gastric metaplasia in the duodenum and the relationship with ulcer recurrence.

OBJECTIVE: To study the prevalence of Helicobacter pylori (H. pylori) infection and gastric metaplasia (GM) in the duodenum a large group of patients with duodenal ulcer was evaluated to determine whether these factors are related to the number of ulcer recurrences. METHODS: Three hundred and seven patients diagnosed by endoscopy as having active duodenal ulcers were studied. At endoscopy, all patients had gastric biopsies taken for histology, the rapid urease test and culture. Three duodenal biopsies were also taken and processed for histology (haematoxylin & eosin, Giemsa, Warthin-Starry, and PAS stain). RESULTS: GM and H. pylori in the duodenum was identified in 73% (68-78%) and 66% (60-71%) of the cases, respectively. All patients with H. pylori in the duodenum also had GM at this location, while areas with GM but without H. pylori were described. The kappa statistic for concordance between GM and H. pylori at the duodenum was 0.82. The prevalence of GM and H. pylori, depending on the number of ulcer recurrences, was: 1st episode, 34% and 27%, respectively; 2nd episode, 84% and 80%; and > or = 3rd episode, 90% and 79% (P < 0.001 when comparing 1st vs 2nd or > or = 3rd episode). In the multivariate analysis, age and number of ulcer recurrences correlated both with GM and with H. pylori in the duodenum. Chronic duodenitis was demonstrated in all duodenal biopsies, 87% being active chronic duodenitis. H. pylori in the duodenum was more frequent in patients with active duodenitis (73%) than in those with inactive duodenitis (13%) (P < 0.001). CONCLUSIONS: Patients with recurrent ulcer disease have a higher prevalence of both GM and H. pylori infection in the duodenum, suggesting that these two factors are related with the chronicity and recurrence of duodenal ulcer disease. H. pylori infection in the duodenum always appears in areas of GM, although GM is not necessarily colonized by the organism. H. pylori infection cannot be excluded based only on the results of duodenal biopsies, as false negative results at this area are frequent.

Adult↗

PubMed2000

A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections.

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sulbactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 microg/ml, respectively), as well as against a beta-lactamase-positive Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 microg/ml) and a beta-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.

Administration, Oral↗

PubMed2000

Ethanol production from glucose and xylose by immobilized Zymomonas mobilis CP4(pZB5).

Fermentation of glucose-xylose mixtures to ethanol was investigated in batch and continuous experiments using immobilized recombinant Zymomonas mobilis CP4(pZB5). This microorganism was immobilized by entrapment in kappa-carrageenan beads having a diameter of 1.5-2.5 mm. Batch experiments showed that the immobilized cells cofermented glucose and xylose to ethanol and that the presence of glucose improved the xylose utilization rate. Batch fermentation of rice straw hydrolysate containing 76 g/L of glucose and 33.8 g/L of xylose gave an ethanol concentration of 44.3 g/L after 24 h, corresponding to a yield of 0.46 g of ethanol/g of sugars. Comparable results were achieved with a synthetic sugar control. Continuous fermentation experiments were performed in a laboratory-scale fluidized-bed bioreactor (FBR). Glucose-xylose feed mixtures were pumped through the FBR at residence times of 2-4 h. Glucose conversion to ethanol was maintained above 98% in all experiments. Xylose conversion to ethanol was highest at 91.5% for a feed containing 50 g/L of glucose and 13 g/L of xylose at a dilution rate of 0.24/h. The xylose conversion to ethanol decreased with increasing feed xylose concentration, dilution rate, and age of the immobilized cells. Volumetric ethanol productivities in the range of 6.5-15.3 g/L.h were obtained. The improved productivities achieved in the FBR compared to other bioreactor systems can help in reducing the production costs of fuel ethanol from lignocellulosic sugars.

Aldose-Ketose Isomerases↗

PubMed2000

Subtypes of intimin among non-toxigenic Escherichia coli from diarrheic calves in Brazil.

One hundred and five strains of Escherichia coli that were isolated from calves with diarrhea in the state of São Paulo, Brazil, and were negative for enterotoxins and cytotoxins, were examined for the eae gene. Four (3.8%) strains were positive by polymerase chain reaction (PCR) and were shown to produce intimin by using Western blot with specific antiserum against the conserved N-terminal region of intimin. Subtyping of the intimins was done by PCR with specific primers and by Western blot with specific antisera against the C-terminal variable region of the protein. Three of these isolates (O?:H11, O26:H-, O123:H1) produced the beta subtype of intimin, and the 4th (0103:H2) produced intimin that was not typable. The 0103:H2 and the O26:H-isolates adhered to HEp-2 cells with diffuse adherence and localized-like adherence patterns, respectively. The other strains did not adhere to HEp-2 cells. To our knowledge, this is the first report of the occurrence of a subtype of intimin described for human enteropathogenic E. coli among bovine diarrheogenic E. coli. It is also the first report from Brazil demonstrating the presence of bovine E. coli harboring the eae gene.

Adhesins, Bacterial↗

PubMed2000

Salivary gland ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom.

In this work we have studied the possible relationships between clinical manifestations such as sialorrhea, appearing in response to the toxic aggression by Tityus discrepans venom, and the alterations or changes at cellular or subcellular levels in sub-maxillary salivary glands in the murine model. To evaluate salivary gland subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: a group of mice were intraperitoneally injected with Tityus discrepans venom at a dose of 5 mg/Kg of weight and controls received saline solution. In the salivary glands from the envenomed animals sub-cellular changes such as hyperchromatic nucleus, swollen rough endoplasmic reticulum, granules of different electron density, some of them practically transparent, nucleolus of low density and big size and electron-transparent cisterns were observed. Capillary wall was augmented in certain areas and thin in others. Endothelial cell infolding to the lumen was seen. The distribution of the vesicles and its density varied. Macrophages and plasmocytes were observed next to the damaged capillaries. Different electron density of cytoplasm was noticed. In conclusion, we suggest that sialorrhea is determined by salivary gland damage produced by toxins present in this venom.

Animals↗

PubMed2000

Neuropathology of bouncer Long Evans, a novel dysmyelinated rat.

BACKGROUND AND PURPOSE: Spontaneous animal mutants affected by abnormal formation of myelin in the central nervous system (CNS) are useful in studies on myelinogenesis and remyelination leading to better understanding of cellular and molecular interactions involved in myelin repair. A novel rat mutant, Bouncer Long Evans (LE-bo) is severely dysmyelinated, but with exceptional longevity, and its clinical and pathologic phenotype are described. METHODS: Clinical observations, genetic studies, and determination of longevity were performed in a colony of rats, including carriers of LE-bo phenotype producing the mutant animals. Comprehensive histologic studies were performed on all perfusion-fixed tissues, and ultrastructural examination of the optic nerve and thoracic part of the spinal cord also was done in rats 1 to 14 weeks old. RESULTS: The LE-bo phenotype is characterized by whole body tremor, progressively severe ataxia, and severe seizure activity. The LE-bo phenotype is transferred as an autosomal recessive trait and is stable. The LE-bo rat can survive in good health beyond 45 weeks. Neuropathologic changes include severe global dysmyelination, with thin uncompacted myelin sheaths in young rats forming no major dense line, whereas the myelin sheaths of the peripheral nervous system appear normal. Oligodendrocytes degenerate with apparently progressing accumulation of membranous material in the perikaryon. Large numbers of immature glial cells were detected in the CNS of LE-bo rats at 4 to 14 weeks. CONCLUSION: The LE-bo rat is severely dysmyelinated due to inability of its oligodendrocytes to form myelin sheaths. Similarities of the LE-bo rat and Long Evans Shaker (les) rat neuropathologic features, such as severe dysmyelination, lack of major dense line in uncompacted myelin sheaths, apparent proliferation of oligodendroglial cells, and considerable longevity, are striking and suggest that a LE-bo mutation may functionally affect the myelin basic protein gene.

Animals↗

PubMed1999

Mutagenicity of thiol compounds in Escherichia coli WP2 tester strain IC203, deficient in OxyR: effects of S9 fractions from rat liver and kidney.

Low doses of L-cysteine (CYS), cysteinyl-glycine (CYSGLY) and reduced glutathione (GSH) activated by gamma-glutamyl transpeptidase (GGT) were mutagenic in strain IC203 (oxyR), whereas higher doses were required to observe a weak mutagenicity in the oxyR+ strain WP2 uvrA/pKM101 (denoted IC188). This indicates that thiol mutagenesis is suppressed by OxyR-regulated antioxidant defenses and confirms its oxidative character. The mutagenesis by low doses of CYS, CYSGLY and GSH + GGT detected in IC203 was abolished by rat liver S9, through the activity of catalase, as well as by the metal chelator diethyldithiocarbamate (DETC), supporting the dependence of this mutagenesis on H2O2 production, probably in thiol autoxidation reactions in which transition metals are involved. Surprisingly, low DETC concentrations greatly potentiate the mutagenicity of low CYS doses. Mutagenesis by high doses of CYS and CYSGLY occurred in both IC203 and IC188 in the presence of liver S9, and was resistant to inhibition by catalase, although it was prevented by DETC. Mutagenesis by GSH activated by rat kidney S9, rich in GGT, was detected in IC203 and IC188 only at high doses since catalase and glutathione peroxidase, both present in kidney S9, might inhibit its induction by low GSH doses. In the presence of liver S9, almost deficient in GGT, GSH was not mutagenic. The mutagenicity of a high GSH dose occurring in the presence either of GGT plus liver S9 or of kidney S9 was weakly prevented by DETC.

Animals↗