Biomedical subjects

M Kundi

Publications and source records attributed to M Kundi.

At least 55 records · Page 3Linked to original sources

PubMed1998

Detection of genotoxic effects of heavy metal contaminated soils with plant bioassays.

Aim of the present study was the development of a bioassay which enables the detection of genotoxic effects of heavy metal contaminated soils. In the first part of the present study, the data base on metal effects in plant bioassays was extended. Four metal salts, namely Cr(VI)O3, Cr(III)Cl3, Ni(II)Cl2 and Sb(III)Cl3 were tested comparatively in MN tests with pollen tetrad cells of Tradescantia clone #4430 and in meristematic root tip cells of Vicia faba. With Cr6+ and Ni2+, clear-cut dose-effects were observed in a range between 0.75 and 10.0 mM, whereas this was not the case with Cr3+ (range tested 1.25-10 mM) and Sb3+ (range 0.30-5.25 mM). In Vicia, negative results were obtained with the four metal salts under all conditions of test. To compare the mutagenic potencies of the metals, the increases of the regression curves (k-values) were calculated, they indicate the number of MN induced per mM in 100 tetrad cells. The corresponding values for Cr6+ and Ni2+ are 0.87 and 1.05, respectively. It appears that the Tradescantia system is in particular sensitive towards those metal species which cause DNA damage in animals and man such as Cr6+, Cd2+, Ni2+, and Zn2+, whereas no clear positive results were obtained with less harmful metal ions such as Cu2+, Cr3+ or Sb3+. In the second part of the study, the mutagenic effects of four metal contaminated soils and two types of standardized leachates (pH 4.0 and pH 7.0) of these soils were tested in Tradescantia and in Vicia. In addition, chemical analyses were carried out to determine the metal concentrations in the soils and in the extracts. Two of the samples contained highly elevated levels of a number of metals (Zn, Pb, Cu, Cd, Sb, As), one soil came from the Central Austrian Alps and contained high As levels only. Direct exposure of the Tradescantia plants in the soils resulted in a drastic increase of the MN frequencies over the background. The lowest effect was seen with the Slovakian soil which contained in particular Sb and As (4.5-fold increase over the background), with the other soils, the induced frequencies were 11-15-fold over the control values. On the contrary, negative results were obtained upon exposure of Tradescantia cuttings in the leachates and upon implantation of germinated Vicia beans in the soils. The results of the present study indicate that Trad-MN assays with direct exposure of intact plants is an appropriate method which enables to detect genotoxic effects of metal contaminated soils in situ. This simple and fast biomonitoring assays might be a valuable supplement to analytical analyses of contaminated soils.

Antimony↗

PubMed1998

Adverse events after oral vaccination against cholera with CVD103-HgR.

The goal of the present study was to evaluate the tolerability and acceptability of an oral cholera vaccine (CVD103HgR) in individuals preparing for travel to countries endemic for cholera. 2545 Austrian travelers between 6 months and 81.5 years of age received a single dose of CVD103HgR and were asked to complete a questionnaire for documentation of adverse events during a 7 day period post immunization. Events were recorded regardless of whether they were caused by concomitant vaccinations or other factors and thus, a causative relationship was not necessarily present. Despite this drawback and the possibility of overreporting this study has proven a low frequency in side effects and the good tolerability of CVD103HgR. Occasional gastrointestinal side effects (15% diarrhea, 8.1% nausea, 1.1% vomiting) were seen and were of mild character and probably a consequence of associated intake of sodium bicarbonate buffer. Other events (7% skin eruptions, 2.7% fever) were mild and considered as harmless (or not vaccine related). The results show that the oral cholera vaccine CVD103HgR was well tolerated and accepted by travelers.

Administration, Oral↗

PubMed1998

Estimated persistence of anti-HAV antibodies after single dose and booster hepatitis A vaccination (0-6 schedule).

The persistence of antibodies after a single dose and booster vaccination against hepatitis A (Havrix 1440) has not yet been assessed. By reanalysing previously published data of serum titres and application of a two-component model, we estimated the duration of protection. In 134 vaccinees, aged 20-39 years, the GMT 1 month after booster was 3629 mlU/ml, which would result in an estimated duration of protection of 34.5 years and in 66 vaccinees aged 40-62 years a GMT of 2320 mlU/ml was calculated, resulting in a duration of protection of 31.5 years. Even when taking the minimum observed titres in the older age group into account, the duration of protection will be more than 10 years. Considering at the same time, its good tolerability and compliance, the single dose hepatitis A vaccination appears highly recommendable in travel medicine.

Adult↗

PubMed1998

Chloracne and morbidity after dioxin exposure (preliminary results).

In this paper, 159 cases of chloracne contamination, reported from 1969 to 1975, in TCDD-contaminated production of the herbicide 2,4,5-trichlorophenol (2,4,5-T) were followed for mortality and morbidity up to 1996, when blood and urine tests were performed on 50 of these chemical workers ('exposed') and matched controls. In exposed workers, the most frequent cause of sick leave was chloracne, which persisted in 32%. Neurological symptoms were reported frequently (44% sleep disturbance, 32% headache, 30% neuralgia). BSR, leucocytes, gamma-GT, S-G0T and S-GPT were significantly higher than in controls. The effects of exposure (P = 0.002) and alcohol (P = 0.002) on gamma-GT were found to be independent of each other.

Acne Vulgaris↗

PubMed1998

Genotoxic effects of heavy metals: comparative investigation with plant bioassays.

The potential use of micronucleus assays in plants for the detection of genotoxic effects of heavy-metal ions was investigated. Three different plant systems were comparatively investigated in micronucleus tests with Tradescantia pollen mother cells (Trad MCN) and micronucleus tests with meristematic root tip cells of Allium cepa and Vicia faba (Allium/ Vicia MCN). As3+, Pb2+, Cd2+, Zn2+ caused a dose-dependent increase of MCN frequencies in all three test systems. Cu2+ gave consistently negative responses in all three tests; Zn2+ caused only a moderate, statistically not significant increase of MCN frequencies in Vicia. The ranking of genotoxic potencies in all three tests was in the descending order: As3+ > Pb2+ > Cd2+ > Zn2+ Cu2+. In experiments with Tradescantia, induction of MCN was observed in a concentration range between 1 and 10 mM, whereas in tests with root tip cells, higher concentrations (10-1,000 mM) were required to show significant effects. Further increase of the exposure levels caused toxic effects (reduction of root growth), cell division delays, and a decrease of MCN frequencies. Comparisons by linear regression analyses indicated that the sensitivity of the three bioassays for heavy metals decreases in the order: Trad MCN > Vicia root MCN > Allium root MCN. In further experimental series, a soil sample which contained high concentrations of the five metals and a control soil were investigated. Aqueous soil extracts induced only weak effects in Trad MCN tests and no effects in the root tip assays, whereas cultivation of the plants in the soils resulted in a pronounced induction of MCN in the Tradescantia system and moderate effects in Vicia and Allium. In conclusion, the results of the study indicate that the Trad MCN assay detects the genotoxic effects of heavy metals and can be used for biomonitoring metal-contaminated soils.

Biological Assay↗

PubMed1997

Improved detection of respiratory syncytial virus in nasal aspirates by seminested RT-PCR.

A seminested RT-PCR for amplification of Respiratory syncytial virus (RSV)-RNA in nasal aspirates has been developed and used to test nasopharyngeal aspirates (NPAs) from 132 infants hospitalized with acute respiratory tract infections during winter epidemics. The results were compared with those obtained by virus isolation in tissue culture and antigen detection with an enzyme-linked immunosorbent assay (Ag-ELISA). RSV-RNA was detected by seminested RT-PCR in 57 of the 59 samples that were positive by virus isolation and/or ELISA, as well as in 25 of 73 samples negative by virus isolation and ELISA. Eighteen of these 25 samples were obtained from children older than one year of age, 17 of whom were experiencing reinfection, as indicated by the presence of preexisting serum RSV-IgG antibodies. These results indicate that seminested RT-PCR is more sensitive than conventional methods for the detection of RSV in patients experiencing reinfections and suggest that this assay might also be useful for rapid diagnosis of RSV infections in older people.

Acute Disease↗

PubMed1996

Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis.

The significance of IgG antibody levels determined by a binding assay (ELISA) was investigated as a surrogate marker for the presence of neutralizing and hemagglutination inhibiting antibodies in sera from individuals vaccinated against tick-borne encephalitis (TBE). To assess the extent of interference by flavivirus cross-reactive antibodies, sera from persons with a proven or suspected history of other flavivirus infections and/or vaccinations were also examined. An excellent and highly significant correlation was found between ELISA IgG units and the antibody titers obtained by the hemagglutination inhibition (HI) as well as by the neutralization test (NT), provided that there was no other exposure to flavivirus antigens except TBE vaccination. Yellow fever vaccination and/or dengue virus infections induced significant levels of antibodies reactive in the TBE ELISA and HI test, which did not exhibit, however, neutralizing activity against TBE virus. The phenomenon and problem of "original antigenic sin" was demonstrated in a TBE vaccinee with a history of previous flavivirus infections. TBE vaccination first induced a booster reaction resulting in a rise in the level of cross-reactive antibodies only, whereas TBE virus-neutralizing antibodies became detectable only after the third vaccination. It is concluded that the level of IgG antibodies determined by ELISA is a good marker for predicting the presence of neutralizing antibodies after TBE vaccination, but only in the absence of flavivirus cross-reactive antibodies. Otherwise, a neutralization assay is necessary for assessing immunity.

Animals↗

PubMed1996

Mutational spectra of Salmonella typhimurium revertants induced by chlorohydroxyfuranones, byproducts of chlorine disinfection of drinking water.

The base substitution specificities of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), and chloromalonaldehyde (CMA), a putative breakdown product of MCA, were examined in the hisG46 gene and in the hisG428 gene of Salmonella typhimurium using allele specific oligonucleotide hybridization. Although the compounds are structurally closely related, they induced substantially different mutation spectra: MCA and CMA caused primarily GC-->AT transitions in the hisG46 allele (target sequence CCC), in particular, at the second position of the codon in strain TA100. In TA100 the mutation spectrum of MCA was similar to that of CMA. The mutational specificity of MCA can be explained as a consequence of misincorporation opposite to cyclic etheno adducts identical to those formed by the carcinogen vinyl chloride. The spectra induced by MX and CMCF in TA100 were almost identical but distinctively different from the spectra of MCA and CMA. Both compounds induced primarily GC-->TA transversions, in particular, at the second position of the codon, and to a lesser extent in the first position of the codon. An identical site bias is induced by carcinogens such as polycyclic aromatic hydrocarbons and heterocyclic amines as a consequence of formation of (noncyclic) guanosine adducts. In hisG428 (target sequence TAA) MX induced again primarily GC-->TA transversions in Tyr tRNA genes (supC/M) and, to a lesser extent, intragenic AT-->TA transversions (TAA-->AAA). The possible involvement of guanosine and adenosine adducts in the mutational specificity of MX is addressed.

Chlorine↗

PubMed1996

Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes.

Mast cells (MC), blood basophils (Ba) and monocytes (Mo) are of haemopoietic origin. Lineage-relationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0.716, 0.779 and 0.757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0.509; MC versus Mo, 0.625; Mo versus Ba, 0.698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R- and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0.2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI = 0.286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)alpha(CD116), CD40, Apo-1/FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)R alpha(CD123), IL-1RII(CD121b), IL-2R alpha(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.

Antigens, CD↗

PubMed1996

Increased inactivation of Saccharomyces cerevisiae by protraction of UV irradiation.

The principle of equi-effectivity of the product of intensity and exposure time (principle of Bunsen-Roscoe) of UV irradiation has been assumed to be valid for the inactivation of microorganisms in general. Earlier studies claimed higher survival of Escherichia coli B/r with fractionated irradiation compared with single-exposure survival. However, data on the inactivation effect of protraction of UV irradiation are not available. By means of a specially designed UV irradiation apparatus which secured absolute UV dose measurements throughout the experiments, the effects of variation of UV irradiation intensities (253.7 nm) and exposure times were tested on the inactivation of a bacterial virus (Staphylococcus aureus phage A994), a vegetative bacterial strain (E. coli ATCC 25922), and bacterial spores (Bacillus subtilis ATCC 6633) as well as three haploid laboratory strains (RC43a, YNN281, and YNN282) and two diploid strains (commercial bakery yeast strain and laboratory strain YNN281 x YNN282) or yeast (Saccharomyces cerevisiae) and spores of the latter diploid yeast strain. Each test organism was exposed to three UV intensities (0.02, 0.2, and 2 W/m2), with corresponding exposure times resulting in three dose levels for each intensity. Differences in inactivation rates were tested by analyses of variance and Newman-Keuls tests. Virus and bacteria showed no differences in inactivation rates by variation of intensities and exposure times within selected UV doses; hence, the principle of Bunsen-Roscoe could not be rejected for these strains. However, in the eukaryotic test strains of S. cerevisiae longer exposure times with lower intensities led to enhanced inactivation in both haploid and diploid strains, with a more pronounced effect in the diploid yeast strains, whereas in yeast spores in this dose rate effect could not be observed.

Bacillus subtilis↗

PubMed1996

Five-year follow-up of patients after thromboendarterectomy of the internal carotid artery: Relevance of baroreceptor sensitivity.

BACKGROUND AND PURPOSE: In patients after myocardial infarction, baroreceptor sensitivity has been identified as a factor of prognostic relevance. This study was designed to assess the effects of an increased baroreceptor sensitivity in patients after surgery in the area of the internal carotid artery with respect to blood pressure variability, therapeutic interventions, and vascular events during a 5-year follow-up. METHODS: Receptor sensitivity before and immediately after carotid surgery was measured in 84 patients. Blood pressure variability, carotid artery status, and echocardiographic findings were assessed before and after surgery and at the end of follow-up. Vascular events as well as changes in blood pressure therapy during the follow-up period were evaluated. RESULTS: Significant negative correlations between an increase of baroreceptor sensitivity after surgery and the range of systolic (r=-.47; P<.001) and diastolic (r=-.33; P<.01) blood pressure were found for the immediate postoperative period. For the range of systolic blood pressure, this relation persisted (4.3 to 7 years after surgery) at the end of the observation period (r=-.38; P<.001). An inverse relation to the increase in baroreceptor function was also found for the average annual number of therapeutic interventions during follow-up (r=-.38; P<.001). Furthermore, the subgroup of patients without a postoperative increase of receptor sensitivity was characterized by a significantly higher risk of major vascular events (log-rank test, P<.018). CONCLUSIONS: Because an improvement of receptor sensitivity after carotid surgery is related to a long-lasting reduction of blood pressure levels and variability, baroreceptor function may be considered an indirect indicator for the later postoperative course.

Aged↗

PubMed1996

Initial prevalence and incidence of secondary Raynaud's phenomenon in patients with Raynaud's symptomatology.

OBJECTIVE: To establish the initial prevalence and incidence of secondary Raynaud's phenomenon (RP) in an outpatient population presenting with RP and assessment of the discriminating and predictive value of the variables of a diagnostic program. METHODS: 112 patients (average followup time 46 mo) were investigated prospectively. A screening program including anamnestic data, clinical examinations, noninvasive angiologic measurements, radiographic examinations, and laboratory chemistry was applied initially and repeated every 6 months. Patients with suspected secondary RP according to the screening underwent an extended diagnostic program. RESULTS: Based on the initial screening, 73 patients were classified as primary RP and 39 patients as suspected secondary RP. After examinations of the extended diagnostic program, 16 patients were diagnosed as secondary RP (initial prevalence 14.3%). During followup another 5 patients were diagnosed as secondary RP (annual incidence 1.4%). Using stepwise logistic regression, 7 screening variables were included in a model, leading to 96% correct classifications (sensitivity 86%, specificity 100%). Most of these variables were also suitable to predict the transition to secondary RP. An alternative classification based on a total symptoms score led to 94% correct classifications (sensitivity 86%, specificity 96%). CONCLUSION: The diagnostic program proved adequate and effective. Patients with RP and related arterial circulatory disorder showed a different clinical course than patients with an immunopathogenesis. A combination of several variables seems to be superior, with respect to the prediction and differentiation of secondary RP, to an approach based on single variables.

Adult↗

PubMed1995

Phorbol-12,13-dibutyrate improves the quality of cytogenetic preparation in lymphoid malignancies.

In cytogenetic preparation of lymphoid malignancies we investigated the quantitative and qualitative impact of phorbol-12,-13-dibutyrate (P) and of this tumor promoter in combination with the calcium ionophore A23187 (PA). Using parallel cultures of unstimulated and stimulated preparations, the effect was examined in 13 patients with malignant lymphomas and six patients with acute lymphoblastic leukemias (ALL). Focusing on high-quality analyzable metaphases, the best results were found in seven of 13 cases with lymphomas and five of six patients with ALL in the cultures supplemented with phorbol-12,13-dibutyrate. The yield of metaphases of good quality regarding length, spreading, and banding of chromosomes was regularly better in P-stimulated 24-hour culture (p < 0.05), followed by 48-hour cultures stimulated with P alone. Addition of the calcium-ionophore was of no further benefit. The yield of the unstimulated direct harvest was rather poor in nearly all patients investigated. Because no mutagenic effect of P was observed, the use of this mitogen may offer interesting perspectives in cytogenetic analysis of lymphoid malignancies and perhaps also in other tumors with low mitotic indexes.

Calcimycin↗

PubMed1995

Effects of macro- and microcirculatory functions on ceftriaxone concentrations in tissues of patients with stage IV peripheral arterial occlusive disease.

The objective of the study was to determine the ceftriaxone levels achievable within lesions (toe or forefoot area) in patients with septic gangrene and to investigate the relationship between macro- and microcirculatory parameters and antibiotic concentration. Fifteen patients with severe chronic peripheral occlusive disease received an intravenous injection of 2 g of ceftriaxone. Antibiotic levels in venous and capillary blood and in an exudative part of the lesion were measured. Macrocirculatory functions were assessed by Doppler sonography, plethysmography, and angiography; microcirculatory functions were assessed by quantitative capillaroscopy and fluorescence video microscopy. The mean antibiotic concentrations measured between 4 and 8 h after injection were 92 +/- 26 micrograms/ml in venous blood and 84 +/- 46 micrograms/ml in capillary blood. The concentration in tissue reached its maximum 4 h after injection; the average concentration at between 2 and 8 h was 95 +/- 55 micrograms/ml. Only dynamic capillary parameters showed significant (P < 0.01) correlations to antibiotic levels in tissue. Significantly (P < 0.01) higher levels in tissue were observed in patients with adequate microcirculatory functions (138 +/- 48 micrograms/ml) than in patients with poor microcirculatory function (51 +/- 26 micrograms/ml). Microcirculatory dysfunction appears to be the limiting factor for tissue antibiotic levels. However, even those patients with poor microcirculatory function showed tissue antibiotic levels that were above the MICs for the pathogens most frequently isolated from gangrenous lesions. Therefore, intravenous application was found to be adequate and additional measures such as intra-arterial therapy or Bier's occlusion are basically unnecessary. Our finding that microcirculatory function is the limiting factor for the tissue antibiotic concentration is corroborated by computations based on a three-compartment model.

Aged↗

PubMed1994

Prevalence of hepatitis-C virus RNA in serum and throat washings of children with chronic hepatitis.

Serum samples from 46 children with chronic and probably transfusion acquired hepatitis were tested for the presence of hepatitis C virus (HCV) RNA by a "nested" polymerase chain reaction (PCR) assay, to judge a possible risk of HCV transmission from these patients. In 73% of the samples, viral RNA was detected, indicating a high virus prevalence in this patient group. High titers of HCV-RNA were observed in some sera as shown by the detection of virus in some samples even at dilutions of 10(-3). Comparison of simultaneously obtained PCR results and ALT values revealed no significant correlation between virus presence in serum and higher ALT levels. It was, however, shown that unusually high ALT values may reflect a high titer of viral RNA in serum. To investigate the prevalence of viral RNA in saliva, which could be a vehicle of virus transmission, 35 throat washing samples from the HCV-infected children were screened by PCR. Using three different sample preparation procedures, 20% of the throat washings were found to be positive for HCV-RNA. This indicates a prevalence of virus in this fluid lower than that reported previously.

Alanine Transaminase↗

PubMed1994

Clinical and immunological investigation of a new combined hepatitis A and hepatitis B vaccine.

As with hepatitis B vaccines, the recently developed hepatitis A vaccine is suitable not only for individual protection, but also for public health control measures. For introduction into routine immunisation programmes, however, hepatitis A vaccine should preferably be combined with other already established vaccines. In particular, a combination of hepatitis A and hepatitis B vaccines would be appropriate. We investigated a new combined hepatitis A/hepatitis B vaccine comparing its tolerability and immunogenicity with that obtained after separate or mixed simultaneous administration of the two components. Three groups of healthy volunteers, each of approximately 50 persons, were included. All were negative for hepatitis A and hepatitis B markers and had normal liver enzyme values. They received hepatitis A (720 ELISA units) and hepatitis B (20 micrograms) vaccines in the deltoid muscle, combined, mixed or separately, according to a 0, 1, 6-month schedule. Blood samples for determination of antibodies to hepatitis A virus (anti-HAV) and hepatitis B virus (anti-HBs) and of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were drawn at months 0, 1, 2, 6, and 7. Local and systemic reactions were monitored by means of questionnaires. The results of our study demonstrate that the combined hepatitis A and B vaccine is well tolerated and highly immunogenic. The seropositivity and seroprotection rates were 100% for both antigens in all groups. Surprisingly, anti-HAV and anti-HBs antibody titres after the combined and mixed vaccines were significantly higher compared with the respective monovalent vaccines injected separately.

Adult↗

PubMed1994

Clastogenic effects of radiofrequency radiations on chromosomes of Tradescantia.

The clastogenicity of electromagnetic fields (EMF) has so far been studied only under laboratory conditions. We used the Tradescantia-micronucleus (Trad-MCN) bioassay in an in situ experiment to find out whether short-wave electromagnetic fields used for broadcasting (10-21 MHz) may show genotoxic effects. Plant cuttings bearing young flower buds were exposed (30 h) on both sides of a slewable curtain antenna (300/500 kW, 40-170 V/m) and 15 m (90 V/m) and 30 m (70 V/m) distant from a vertical cage antenna (100 kW) as well as at the neighbors living near the broadcasting station (200 m, 1-3 V/m). The exposure at both sides of the slewable curtain antenna was performed simultaneously within cages, one of the Faraday type shielding the field and one non-shielding mesh cage. Laboratory controls were maintained for comparison. Higher MCN frequencies than in laboratory controls were found for all exposure sites in the immediate vicinity of the antennae, where the exposure standards of the electric field strength of the International Radiation Protection Association (IRPA) were exceeded. The results at all exposure sites except one were statistically significant. Since the parallel exposure in a non-shielding and a shielding cage also revealed significant differences in MCN frequencies (the latter showing no significant differences from laboratory controls), the clastogenic effects are clearly attributable to the short-wave radiation from the antennae.

Chromosome Aberrations↗

PubMed1994

Effects of ethanol treatment on DNA damage induced in Escherichia coli K-12 in various organs of mice by N-nitro-sonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosopyrrolidine.

DNA damage induced by tobacco-related nitrosamines was quantitatively determined in animal-mediated DNA-repair assays with Escherichia coli K-12 strains. Intraperitoneal administration of N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosopyrrolidine (NPYR) caused dose-dependent genotoxic effects in indicator bacteria recovered from various organs of nitrosamine-pretreated mice. Oral administration of ethanol (6.3 g/kg body wt) 1 h prior to administration of NNN, NNK or NPYR resulted in a substantial reduction of genotoxicity that was more pronounced in the liver as compared to lungs, spleen, kidneys and blood. However, when the same ethanol dose was given 26 h before NNN or NPYR, an increase of DNA damage was found, that was, in most cases, higher in the kidneys than in the liver. Significant enhancement of genotoxic activity was also measured in lungs and spleen, whereas only a marginal increase was detectable in the blood. Repeated administration of smaller ethanol doses (2.0 g/kg body wt at 12 h intervals) for 4 days caused a comparable increase. Similar enhancement of genotoxicity was also measured when acetone (3.5 g/kg) was given orally 15 h before the nitrosamine administration. The stimulating effect of ethanol was dose dependent and was absent when the alcohol was administered 60 h prior to the nitrosamine. Neither ethanol nor acetone had an effect on the genotoxicity of NNK under identical experimental conditions. The same E. coli K-12 strains were used to test NNN, NNK and NPYR in in vitro assays. The ranking order of activation capacity was liver S-9 > kidney S-9 > lung S-9 for all three nitrosamines. Blood S-9 did not markedly activate the nitrosamines. S-9 mixtures prepared from mice that had been treated with ethanol (6.3 g/kg body wt) for 26 h before death activated NNN and NPYR more efficiently than those S-9s from untreated animals. The increase of genotoxic activity was more pronounced with S-9 from kidneys and lungs than from liver. No difference was seen with S-9 from ethanol-treated and untreated mice with NNK.

Animals↗