Megakaryocytic cell line-specific hyperploidy by cytotoxic necrotizing factor bacterial toxins

1996

Cytotoxic necrotizing factor (CNF) toxins, isolated from certain Escherichia coli strains known to cause intestinal and extra intestinal infections, induce reorganization of the actin cytoskeleton and generate hyperploidy in adherent cell lines. We have examined the effect of CNF toxin on one of the few cell types that naturally increase nuclear DNA content, megakaryocytes. Our studies show that only hematopoietic cells capable of differentiating along the megakaryocyte lineage responded to the CNF2 toxin by becoming polyploid and by reorganizing actin. The K562, HEL, and CHRF-288–11 cell lines can be induced with phorbol ester to differentiate along the megakaryocyte lineage, and these cel…

Nonresonant Spectral Hole Burning in the Slow Dielectric Response of Supercooled Liquids

1996

Large-amplitude, low-frequency electric fields can be used to burn spectral holes in the dielectric response of supercooled propylene carbonate and glycerol. This ability to selectively modify the dielectric response establishes that the non-Debye behavior results from a distribution of relaxation times. Refilling of the spectral hole was consistent with a single recovery time that coincided with the peak in the distribution. Moreover, refilling occurred without significant broadening, which indicates negligible direct exchange between the degrees of freedom that responded to the field. Nonresonant spectral hole burning facilitates direct investigation of the intrinsic response of systems t…

Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2 therapy

1996

Viña, José, Emilio Servera, Miguel Asensi, Juan Sastre, Federico V. Pallardó, José A. Ferrero, JoséGarcı́a-de-la-Asunción, Vicente Antón, and Julio Marı́n. Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2therapy. J. Appl. Physiol. 81(5): 2199–2202, 1996.—The aim of the present study was to determine whether glutathione oxidation occurs in chronic obstructive pulmonary disease (COPD) patients who perform exercise and whether this could be prevented. Blood glutathione red-ox ratio [oxidized-to-reduced glutathione (GSSG/GSH)] was significantly increased when patients performed exercise for a short period of time until exhaustion. Their res…

Organometallic nucleophiles.A mechanistic study of halide displacement at saturated carbon by 2- and 4-pyridyl complexes of palladium (II) and platin…

1996

Abstract The reactions of the 2- and 4-pyridyl complexes [MX(C 5 H 4 N C n )(dppe)] and trans -[MX(C 5 H 4 N C n )(PPh 3 ) 2 ] (M  Pd, Pt; X  Cl, Br; n = 2, 4)- involving halide displacement from the organic halides XCH 2 R (X  Cl, Br; R  CN, Ph, CH  CH 2 ) by the pyridyl nitrogen have been studied kinetically by conductivity in acetone or acetonitrile at 25°C. The kinetic data fit the second-order rate law rate k 2 [XCH 2 R][complex], in agreement with an S N 2 process at saturated carbon. The higher rates are displayed by the 2-pyridylplatinum derivatives with X  Br in both the metal complex and the organic halide. The higher nucleophilic power of the 2-pyridyl complexes compare…

Definition of the single integration site of the pathogenicity locus in Clostridium difficile.

1996

We determined the nucleotide sequence 3.8 kb upstream and 5.2 kb downstream of the toxin genes A and B of Clostridium difficile. Nine ORFs were discovered. Based on PCR-directed approaches, two were attributed to the pathogenicity locus (PaLoc). The other seven were found in every C. difficile isolate obtained from the human gastrointestinal tract, respectless of their toxinogenicity. The ORFs cdu1 and cdu2/2' upstream of the PaLoc displayed similarity to repressors of Gram-positive bacteria (cdu1), and to an Na+/H+ antiporter described for Enterococcus hirae (cdu2/2'). Downstream of the locus a putative ABC transporter (cdd2-4) was identified. With a set of three paired primers used in pol…

Aroma compounds in wine as influenced by apiculate yeasts

1996

Aroma compounds of wines resulting from fermentation of sterile grape musts from Monastrell variety inoculated with pure and mixed cultures of apiculate and Saccharomyces yeasts, were isolated and analyzed by gas chromatography with flame ionization and mass spectrometry. Samples fermented with mixed cultures produced a higher concentration of selected compounds and higher total amounts of alcohols and acids, in contrast with wines produced with pure cultures of Saccharomyces spp. Apiculate yeasts are important in the chemical composition and quality of wine.

The mouseClq genes are clustered on chromosome 4 and show conservation of gene organization

1996

Mouse complement component C1q is a serum glycoprotein which consists of six A chains, six B chains and six C chains. The three polypeptides are 223, 228, and 217 residues long, respectively, and are encoded by three genes. DNA probes for mouse C1q A, B, and C chains were hybridized to Southern blots of DNA obtained from various inbred mouse strains. On the basis of fragment length polymorphisms, two different alleles of each of the genes could be identified. The distribution of these alleles was determined in the BXD and LXPL recombinant inbred strain series. Comparison with previously reported strain distribution patterns shows that the genes encoding mouseClq map to the same locus on dis…

Die Röntgenstrahlenbelastung der Hände der Operateur bei Marknagelosteosynthesen

1996

Bei 41 Marknagelungen (21 unaufgebohrte und neun aufgebohrte Tibiamarknagelungen sowie vier unaufgebohrte und sieben aufgebohrte Femurmarknagelungen) trugen Operateur und 1. Assistent Ringdosimeter am dominanten Zeigefinger unter dem sterilen Handschuh. Bei Durchleuchtungszeiten von durchschnittlich 4.6 min pro Eingriff lag die mittlere Strahlenbelastung der Finger der Operateur bei 1.27 mSv und die der 1. Assistenten bei 1,19 mSv. Extrapoliert man den Gesamtmittelwert der ermittelten Strahlenbelastung der Hand der Operateure und 1. Assistenten von 1,23 mSv, wurde der gesetzlich zugelassene Grenzwert fur beruflich strahlenexponierte Personen der Gruppe A von 500 mSv erst bei 407 Marknagelos…

Chronic toxicity of fenitrothion to an algae (Nannochloris oculata), a rotifer (Brachionus calyciflorus), and the cladoceran (Daphnia magna).

1996

Chronic toxicity studies were conducted with an algae (Nannochloris oculata), a rotifer (Brachionus calyciflorus), and a cladoceran (Daphnia magna) to determine their relative sensitivities to the organophosphorus insecticide fenitrothion. The cladoceran D. magna was the most sensitive of the three species. The no observed effect concentrations (NOECs) for the study with the algae (1.0 mg/liter) and for the rotifer (1.0 mg/liter) were higher than the NOEC (0.009 microgram/liter) and the LC50 of 24 hr (0.067 microgram/liter) for D. magna. Most of the algal populations were not initially affected by exposure to fenitrothion. Pesticide concentrations higher than 1.0 mg/liter significantly redu…

Molecular dynamics in liquid crystalline N-acylated oligoethylenimines as studied by broadband dielectric spectroscopy

1996

The molecular dynamics and the charge transport in six liquid crystalline N-acylated oligoethylenimines were investigated by dielectric spectroscopy. The dielectric spectra in the temperature range from 125 K up to 400 K and in the frequency range between 10 -2 Hz and 10 7 Hz could be described by a conductivity contribution and three relaxation processes. The molecular assignment of the α-process is a relaxation of the rigid benzamide unit. Its mean relaxation time is influenced by the length of the alkoxy side chains, the spacer length (ethylene or propylene groups) and the neighboring repeating units. In the columnar mesophase this process is cooperative due to sterical hindrance. A norm…

The egoistic approach to parallel process migration into heterogeneous workstation network

1996

Abstract A new approach to the allocation of processes in a distributed system is discussed. The proposed solution deals with process migration into heterogeneous systems by means of a strategy that delegates the individual parallel applications to manage the migration of their processes by themselves, on the basis of their own performance objectives. This approach is discussed in opposition to the global scheduling based one, and the load balancing objective is pursued as an effect of the optimization of individual applications. A new performance evaluation criterion is introduced that consists in monitoring the delays that occur when two parallel processes run towards a common synchroniza…

Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging.

1996

To assess the feasibility of helium-3 magnetic resonance (MR) imaging with a three-dimensional fast low-angle shot (FLASH) sequence, He-3 gas (volume, 300 mL; pressure, 3 x 10(5) Pa; polarized up to 45% by means of optimal pumping) was inhaled by five healthy volunteers and five patients with pulmonary diseases. All breath-hold examinations (22-42 seconds) were completed successfully. Normal ventilation was depicted with homogeneous high signal intensity, lesions were depicted as causing defects, and obstructive lung disease was depicted with severely inhomogeneous signal intensity.

Quantitative analysis of mixtures of metal-carbonyl complexes by Fourier-transform infrared spectroscopy: application to the simultaneous double immu…

1996

Abstract The feasibility of a double immunoassay of haptens by the nonisotopic carbonyl metalloimmunoassay (CMIA) method is demonstrated. Three different pairings of antiepileptic medications from the groups carbamazepine, diphenylhydantoin, and phenobarbital (for each of which a mono-CMIA is already available) were assayed by double CMIA. The assay method employs as tracers metal–carbonyl complexes that give very strong signals in the range of 1850–2200 cm −1 in the infrared spectrum, permitting quantitative analysis by Fourier-transform infrared spectroscopy. The fact that the signals are individually assignable and of comparable intensity permits quantitative analysis of mixtures of two …

HPLC Method for Cyst(e)ine and Methionine in Infant Formulas

1996

Cyst(e)ine and methionine were converted into cysteic acid and methionine sulfone by oxidizing with performic acid. The oxidized samples were then subjected to acid hydrolysis (6N HCl, 105-110°C/24 hr). After derivatization with phenylisothiocyanate, reverse phase HPLC separation was carried out at 48°C and with UV detection. Different gradients and pH values in the eluent were assayed to determine the best resolution. Analytical parameters, detection and quantification limits, linearity, precision and accuracy, were determined. The method was reliable and accurate for measuring cyst(e)ine and methionine in infant formulae.

Effects of vasopressin on human renal arteries

1996

The effects of vasopressin were studied in isolated rings from branches (2-3 mm in external diameter) of human renal arteries obtained from 18 patients undergoing nephrectomy for non-obstructive neoplasia. In arterial rings under resting tension, vasopressin produced concentration-dependent and endothelium-independent contractions with an EC 50 of 9.1 x 10 -10 mol L -1 . The vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 -6 mol L -1 ) displaced the control curve to vasopressin 564-fold to the right in a parallel manner. In precontracted arterial rings and previously treated with the V 1 antagonist (10 -6 mol L -1 ) vasopressin caused endothelium-independent relaxation. The re…

Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants

1996

Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of h…

OnF-Subnormal Subgroups andF-Residuals of Finite Soluble Groups

1996

All groups that we consider are finite and soluble. Recall that a formation is a class of groups which is closed under homomorphic images and subdirect products. Hence, if F is a formation and G is a group which is a direct product of the subgroups A and B, then G is in F if and only if A and B lie in F. More generally, Doerk and w x Hawkes 4, IV, 1.18 proved that if G is a group such that G s A = B, then G s A = B , where G is the F-residual of G, that is, the smallest normal subgroup of G with quotient in F. The main purpose of this paper is the development of this result by means of the concept of F-subnormal subgroup. Suppose that F is a saturated formation. A maximal subgroup M of a Ž …

Ab initio study of the internal rotation potential of p-disilanylbenzene and p-(1,1′,2,2′-tetramethyldisilanyl)benzene

1996

Abstract We present a detailed ab initio study of the geometrical structure and torsional potential of p -disilanylbenzene and its methyl derivative p -(1,1′,2,2′-tetramethyldisilanyl)benzene. The geometries of the different conformers have been fully optimized at the Hartree-Fock 3-21G ∗ and 6-31G ∗ levels. In all cases, the most stable conformation corresponds to the conformer in which the phenylene group lies in a plane perpendicular to the four silicon atoms. The torsional potential curves calculated using the 3-21G ∗ and 6-31G ∗ basis sets show similar features. In the case of p -(1,1′,2,2′-tetramethyldisilanyl)benzene the interactions between the hydrogen atoms of phenylene and the me…

Glutathione Transferase A1-1 Catalyzed Conjugation of Polycyclic Aromatic Hydrocarbon Diol-Epoxides with Glutathione

1996

Abstract The glutathione transferase A1-1 (GSTA1-1) isoenzyme catalyzes the formation of GSH-conjugates of the isomeric bay-region diol-epoxides (DEs) of trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene (CDE) and trans-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,h]anthracene (DBADE) as well as the isomeric fjord-region DEs trans-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BPhDE) and trans-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-benzo[c]chrysene (BCDE) although with an approx. 20-fold variation in catalytic efficiency. With the anti-diastereomers and the syn-diastereomers of BPhDE and BCDE, GSTA1-1 demonstrated a significant preference for the enan…

Genetic basis of speed of development in Senecio vulgaris L var. vulgaris, S. vulgaris ssp. denticulatus (O.F. Muell.) P.D. Sell, and Senecio vernali…

1996

The genetic basis of differences in speed of development from germination to first bud formation was investigated in Senecio vulgaris var. vulgaris and S. vulgaris ssp. denticulatus, and also in S. vernalis sampled from Israel and Germany. In the case of S. vulgaris, F2 segregation analysis and the recovery of very late and very early lines from extreme F2 phenotypes showed that differences can be explained by a single major gene model, whereas segregation data from F2 and backcross progenies in S. vernalis are not incompatible with a digenic model of inheritance. Senecio vernalis from Israel and S. vulgaris var. vulgaris reached the different developmental stages in a substantially shorter…

Optimization of a matrix solid-phase dispersion method for the analysis of pesticide residues in vegetables

1996

A multiresidue method based on matrix solid-phase dispersion (MSPD) is studied to determine chlorfenvinfos, chlorpyrifos, fenarimol, iprodione, procimydone, propiconazole, tetradifon, triadimefon and vinclozolin in artichokes, green beans, lettuces and tomatoes. Alumina, silica and Florisil were assessed as extracting phases, and the extracts from Florisil were the cleanest. To facilitate manual extraction, sand was added to the sample together with the dispersing phase. Three eluting systems were then studied, and dichloromethane proved to be the best. Further purification can be performed using solid-phase cleanup after diluting extracts with aqueous solutions. Octyl- and octadecyl-silica…

Networks of Partially Hydrogenatedcis-1,4-Polybutadiene and ‘Rigid Rods’

1996

Networks of 'flexible' and 'rigid' chains were synthesized. As 'flexible' component we have used different partially hydrogenated cis-1,4-polybutadiene. The 'rigid' component was synthesized from bis(1,2,4-triazoline-3,5-dione)s and biscyclohexadienes via repetitive Diels-Alder reaction. A slight excess of bis(1,2, 4-triazoline-3,5-dione)s leads to polymers with 1,2,4-triazoline-3,5-dione end groups, which can easily react with the partially hydrogenated cis-1,4-polybutadiene. The influence of the extent of hydrogenation and the amount of crosslinker on the mechanical and thermal behaviour is described.

Long-Term Follow-Up of Patients with Chronic Hepatitis C after Interferon-Alpha Treatment

1996

In this study, 72 patients with chronic hepatitis C virus (HCV) were followed prospectively for a mean period of 27 months after interferon treatment. Fifty-seven percent (20/35) of the patients with complete response, 18/20 with HCV-RNA-negative serum, had a sustained biochemical remission. Reactivation was seen in 43% of these patients after a mean follow-up of 7.3 months. A late relapse after more than 12 months of follow-up occurred in only 2/15 patients. Patients with a long-term complete response had significantly lower pretreatment serum HCV RNA levels than complete responders with relapse (106,239 vs. 345,649 mEq/ml, p = 0.0213). A delayed sustained biochemical remission was seen in…

Ductility of garnet as an indicator of extremely high temperature deformation: Discussion

1996

Detection of Reactive Quinones in the Metabolism of Polycyclic Aromatic Hydrocarbons by the Formation of their Glutathione Conjugates

1996

Abstract The biotransformation of polycyclic aromatic hydrocarbons to quinones by rat liver microsomes was investigated. The employment of an electrochemical detector allowed the specific detection of quinones separated by reverse phase HPLC with higher sensitivity as compared to UV detection. Microsomal incubations of benzo[a]pyrene (BP) resulted in the formation of 1,6-, 3,6- and 6,12-quinones, of naphthalene in the detection of naphthalene-1,4-quinone, whereas ortho-quinones could only be detected in trace amounts. Additional protein binding studies showed that only 9–22% of synthetic ortho-quinones could be recovered from microsomal incubations. In order to scavenge possible reactive qu…

Oxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18 and 2C19. Evidence that this drug is a mechanism-based inhibitor…

1996

Oxidation of tienilic acid by human cytochromes P-450 (CYP) 2C9, 2C18, 2C8 and 2C19 was studied using recombinant enzymes expressed in yeast. CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid (K(m) = 5 +/- 1 microM, kcat = 1.7 +/- 0.2 min-1), 30-fold more potent in terms of kcat/K(m) than CYP 2C18 (K(m) = 150 +/- 15 microM, kcat = 1.8 +/- 0.2 min-1) and 300-fold more potent than CYP 2C8 (K(m) = 145 +/- 15 microM, kcat = 0.2 +/- 0.1 min-1). CYP 2C19 was unable to catalyze this hydroxylation under our experimental conditions. During this study, a marked effect of the ionic strength on the activities (hydroxylations of tienilic acid and tolbutamide) of these cytochromes P-450 …

EPR, ENDOR and TRIPLE resonance of amino-substituted 9,10-anthraquinone radicals and the rotation of the amino groups in the solution phase

1996

EPR, ENDOR and TRIPLE resonance spectra were recorded for 1-amino-9,10-anthraquinone (1-aminoAQ), 2-aminoAQ, 1,2-diaminoAQ, 1.4-diaminoAQ, 1,5-diaminoAQ and 2,6-diaminoAQ anion radicals in the solution phase. The rotation of the amino groups is discussed with reference to the experimental data. Rotation barrier calculations were carried out using B3PW91/3-21G* density functional method. The amino groups at positions 1, 4, 5, 8 were found not to be in rotational movement up to the EPR time-scale.

Postrenal anuria in pelvic or acetabular injury: a report of three cases.

1996

Renal failure due to obstruction by a retroperitoneal hematoma is a rarely discussed complication in pelvic or acetabular fractures. Three cases of this obstructive uropathy are presented. They were successfully treated with removal of the hematoma and draining of the retroperitoneal space.

The capacity of liver microsomes to form benzo[a]pyrene-diolepoxide-DNA adducts and induction of cytochrome P450 1A in feral fish exposed to pulp mil…

1996

An investigation was made of cytochrome P4501A (CYP1A) induction, determined by the activity of EROD (7-ethoxyresorufin O-deethylase), and formation of benzo[a]pyrene-diolepoxide-DNA (BPDE-DNA) adducts, measured by synchronous fluorescence spectrophotometry, in liver microsomes of perch (Perca fluviatilis), bream (Abramis brama), and roach (Rutilus rutilus). Fish were collected from the southern part of Lake Saimaa (Finland), an area polluted by effluents from the pulp and paper industry. In addition, two conjugation enzymes (UDP-glucuronosyltransferase and glutathione S-transferase) were determined. Overall, when compared to an upstream reference, EROD activity was higher in fish at waters…

Triangle amplitude with off-shell CoulombTmatrix for exchange reactions in atomic and nuclear physics

1996

The lowest-order rescattering contribution (triangle amplitude) in three-body models of exchange reactions with charged particles contains the off-shell two-body T matrix describing the intermediate-state Coulomb scattering of charged subsystems. General properties of the exact exchange triangle amplitude, when the incoming and outgoing particles are on the energy shell, are derived. This includes the analytic behavior, i.e., the positions and characters of its leading singularities, in the cos\ensuremath{\vartheta} plane, where \ensuremath{\vartheta} is the scattering angle, in the vicinity of the forward- and backward-scattering directions. Since for computational reasons the Coulomb T ma…

Hydrophobic effects in the stabilisation of copper(I) by the macrocyclic ligands 16,17,19,20-tetramethyl-2,6,9,13-tetraaza[14]paracyclophane and 14,1…

1996

Abstract The interaction of Cu 2+ with the para -azacychlophanes 16,17,19,20-tetramethyl-2,6,9,13-tetraazal[14]paracyclophane (L1) and 14,15,17,18-tetramethyl-2,5,8,11-tetraaza[12]paracyclophane (L2) has been studied by potentiometry, and direct microcalorimetry at 298.1±0.1 K in 0.15 mol dm −3 NaClO 4 . The stability constants (log K CuLi = 13.35(3), log K CuL2 = 9.32(4)) and the thermodynamic parameters ( ΔH ° CuL1 = −47.3(8) kJ mol −1 , ΔH ° CuL2 = 20.9(8) kJ mol −1 ) evidence that not all four nitrogen atoms in the ligands are involved in the coordination to the metal centre. These results, particulary in the case of L1, are similar to those reported for the analogous cyclophanes contai…

Multiplicity of solutions for two-point boundary value problems with asymptotically asymmetric nonlinearities

1996

Ethoxyresorufin-O-deethylase induction potency of polychlorinated diphenyl ethers in H4IIE rat hepatoma cells

1996

Polychlorinated diphenyl ethers (PCDEs) are structurally similar to polychlorinated biphenyls (PCBs), and some PCDE congeners have been reported to cause toxic responses similar to those caused by some of the non-ortho-substituted PCBs, which are mediated by the aryl hydrocarbon receptor (AhR). Twenty-nine PCDEs were tested for their potency as AhR agonists relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) by measuring their ability to induce the cytochrome P-450 1A1-associated enzyme activity, ethoxyresorufin-O-deethylase (EROD), in the H4IIE rat hepatoma cell bioassay. All PCDE congeners tested were found to be inactive as EROD inducers except for PCDE 156, which was a weak E…

Medium-range interactions and crossover to classical critical behavior

1996

We study the crossover from Ising-like to classical critical behavior as a function of the range R of interactions. The power-law dependence on R of several critical amplitudes is calculated from renormalization theory. The results confirm the predictions of Mon and Binder, which were obtained from phenomenological scaling arguments. In addition, we calculate the range dependence of several corrections to scaling. We have tested the results in Monte Carlo simulations of two-dimensional systems with an extended range of interaction. An efficient Monte Carlo algorithm enabled us to carry out simulations for sufficiently large values of R, so that the theoretical predictions could actually be …

Vibrational Properties of InSe under Pressure: Experiment and Theory

1996

The pressure dependence of the phonon modes in the layered semiconductor γ-InSe has been investigated experimentally and theoretically for pressures up to 11 GPa. The mode Gruneisen parameters of all Raman-active zone-center phonons have been determined by Raman scattering under pressure. In addition, features corresponding to second and third-order scattering processes are apparent in the Raman spectra under resonance conditions, from which information about zone-edge modes can be obtained. For the assignment of the observed Raman features to vibrational modes we have calculated the phonon dispersion curves using a rigid-ion model including couplings to first-nearest neighbors and long-ran…

Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis

1996

The single cell gel test (SCG-test or comet assay) is a rapid and sensitive method for measuring DNA damage and repair in individual cells. A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations. We are therefore investigating in a cell culture system with human cells (MRC5CV1) the induction of DNA damage by environmental mutagens and the formation of mutations at the HPRT gene. In the present study we investigated benzo[a]pyrene (BP), an environmental mutagenic and carcinogenic polycyclic aromatic hydrocarbon, and its reactive metabolite…