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Biomedical subjects

B Lambert

Publications and source records attributed to B Lambert.

At least 163 records · Page 9Linked to original sources
PubMed1983

Genetic toxicity of dopamine.

The genetic toxicity of dopamine was studied in a battery of test systems including DNA single-strand break analysis in cultured human skin fibroblasts, the Salmonella/mammalian-microsome mutagenicity test, sister-chromatid exchange analysis in human lymphocytes, the mouse-lymphoma forward mutation assay, the sex-linked recessive lethal test in Drosophila melanogaster and the micronucleus test in mouse and rat. Dopamine at concentrations of 50-300 micrograms/ml induced DNA strand breaks in human fibroblasts. It also gave a positive response in the mouse-lymphoma forward mutation assay, where a dose-dependent increase in the frequency of mutant cells was observed in the presence of dopamine, 94-750 micrograms/ml. All other tests showed no response to dopamine. The dopamine-induced DNA strand breaks in human fibroblasts were inhibited by superoxide dismutase or dithiothreitol. Furthermore, dopamine caused nicking of circular Col El DNA and bound to calf thymus DNA in vitro. It is suggested that this genetic activity of dopamine in vitro relates to oxidation of dopamine and the generation of reactive oxygen radicals, semiquinones and quinones. It is unlikely that similar reactions would occur and cause genotoxic activity of dopamine in vivo.

Animals↗
PubMed1983

Induction and reduction of sister chromatid exchange by CCNU in human lymphocytes in vitro.

Sister chromatid exchange (SCE) was studied in human lymphocytes treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in vitro. A dose-dependent increase of SCE was observed in cells exposed to 10(-5) - 10(-4) M CCNU. The maximal increase was 25-35 SCEs/cell over the control level, which is similar to the increase found in patients treated with CCNU in vivo. In the presence of rat liver microsomes (S-9 fraction) the frequency of CCNU-induced SCE was slightly higher than in parallel cultures without S-9, suggesting that microsomal metabolism may enhance the rate of decomposition of CCNU into reactive products. The CCNU-induced increase of SCE was greater in cells treated for longer time periods (up to 70 hr) than in cells subjected to a 1-hr treatment. This effect was most pronounced at higher concentrations of the drug (5 X 10(-5) M). The frequency of CCNU-induced SCE was also found to be dependent on the time of treatment in the cell cycle. A treatment for 1 hr during early G1-phase (about 20 hr before the first S-phase) gave rise to a higher increase of SCE than a 1 hr treatment immediately before or during the first or second S-phase. Thus, the CCNU-induced DNA damage leading to SCE seems to persist and may even increase during the prereplicative phase of the cell cycle. After replication in BrdUrd-free medium, the frequency of CCNU-induced SCEs decreased to the control level. The present results, taken together with other studies of strand break and cross-link formation by CCNU in mammalian cells in vitro, suggest that the major SCE-inducing damage by CCNU is DNA interstrand cross-links. These lesions then appear to be slowly removed, if at all, during the prereplicative phase of the cell cycle, and to disappear during or after replication in BrdUrd-free medium in vitro.

Biotransformation↗
PubMed1983

Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation.

Exposure of human lymphocytes and skin fibroblasts in vitro to a single, clinically used dose of PUVA, i.e., 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 0.9-4 J/cm2 of longwave ultraviolet radiation (UVA), lead to the formation of DNA damage as determined by alkaline elution, and to chromosome aberrations and sister chromatid exchanges (SCE). When lymphocyte-enriched plasma was obtained from psoriasis patients 2 h after oral intake of 8-MOP and then UVA irradiated (1.8-3.6 J/cm2) in vitro, an increased frequency of chromosome aberrations and SCE was observed. Normal levels of chromosome aberrations and SCE were found in lymphocytes of psoriasis patients after 3-30 weeks of PUVA treatment in vivo. A small but statistically significant increase in the SCE frequency was observed in the lymphocytes of psoriasis patients treated for 1-6 years with PUVA (mean 18.0 SCE/cell) as compared with before PUVA (mean 15.8, p less than 0.05). Skin fibroblasts of psoriasis patients analyzed 5 years after the start of PUVA treatment showed a normal number of SCE but a high fraction of filter-retained DNA in the alkaline elution assay, suggesting the presence of cross-linked DNA.

Chromosome Aberrations↗
PubMed1982

Late side effects of chemotherapy in ovarian carcinoma: a cytogenetic, hematologic, and statistical study.

Late side effects of chemotherapy were studied in 51 women who had received at least 300 mg of melphalan for ovarian cancer and had survived for at least three years. Hematologic, statistical, and cytogenetic methods were employed. Six cases of iatrogenic leukemia were found. They appeared to represent a hematologic entity that is fairly difficult to recognize. The risk of iatrogenic leukemia in women who survived for three years or more after melphalan treatment was calculated to be 950 times greater than the leukemia risk in the total female population. The cytogenetic changes were studied with three methods focused on sister chromatid exchange, chromosome aberrations, and DNA damage. The sister chromatid exchange frequency showed a marked increase, but it was corrected within a few months. Chromosome aberrations expressed by chromosome rearrangements were increased in the peripheral lymphocytes and may persist for several years. The frequency of DNA stand breaks was decreased indicating the presence of DNA cross-links. Any of these types of genetic alteration could be the initiating event in carcinogenesis.

Acute Disease↗
PubMed1982

[Isolation and characterization of Escherichia coli strains sensitive to hydrophilic and/or charged antibiotics and toxics (author's transl)].

Two Escherichia coli mutant strains sensitive to antitumor derivatives of ellipticinium, ethidium bromide and to a variety of hydrophilic antibiotics and toxics have been isolated. The two mutations have been mapped on the bacterial chromosome at 5 +/- 1 and 10 +/- 1 mn respectively. Some properties of these strains are described and their interest in mutagen testing is discussed.

Anti-Bacterial Agents↗
PubMed1982

Induction and repair of psoralen cross-links in DNA of normal human and xeroderma pigmentosum fibroblasts.

Skin fibroblasts from normal human subjects were exposed in vitro to long-wave ultraviolet radiation (UVA, 320-400 nm) alone, or in combination with 8-methoxypsoralen (8-MOP). DNA damage was analysed with the alkaline elution technique before and after post-treatment incubation of the cells at 37 degrees C for various times. Cells treated with UVA at 1.1 J/cm/ showed an increased DNA elution rate, which returned to the normal level within 30 min of post-treatment incubation. In cells treated with PUVA (8-MOP at 20 microgram/ml plus UVA at 0.04 J/cm2), the alkaline elution rate was not different from untreated control cells, either before or after post-treatment incubation for time up to 7 days. When the PUVA treatment was followed first by a washing, to remove any unbound 8-MOP, and then by UVA (PUVA + UVA) at 1.1 J/cm2, the alkaline elution rate decreased below the control level. During the post-treatment incubation of the PUVA + UVA-treated cells there was a gradual increase of the alkaline elution rate to a level significantly above that in control cells. This increase was observed after 30 min. It reached a maximum after 24 h and remained after 7 days of post-treatment incubation. Cells from a patient with xeroderma pigmentosum of complementation group A, which were given the same PUVA + UVA treatment, did not show any change in the alkaline elution rate during the post-treatment incubation. If, as seems likely, an increased alkaline elution rate indicates as increase of DNA breaks, and a decreased alkaline elution rate indicates the sealing of breaks and/or the formation of cross-links, and results would suggest the following: (1) UVA irradiation in itself is capable of inducing DNA breaks, which are rapidly sealed during post-treatment incubation; (2) PUVA treatment induces mono-adducts, some of which appear to remain in the DNA for at least 7 days of post-treatment incubation and can be activated to form DNA cross-links by a second dose of UVA; (3) DNA cross-links induced by PUVA + UVA can be recognized by a repair process that involves the formation of DNA breaks. This process is not observed in xeroderma pigmentosum cells of group A.

Cell Line↗
PubMed1982

DNA and chromosome alterations in lymphocytes of operating room personnel and in patients before and after inhalation anaesthesia.

In order to evaluate the possible genotoxic effects of inhalation anaesthetics, the frequency of sister chromatid exchanges and chromosome aberrations was studied in peripheral lymphocytes of control subjects, operating room personnel and patients before and after inhalation anaesthesia during orthopaedic operations. In the patients, the frequency of DNA breaks was studied as well. None of the genotoxic parameters showed an increase which could be related to anaesthetic exposure. The frequency of sister chromatid exchange was very similar in the control and personnel groups, as well as in patients before and after operation. The frequency of chromosome aberrations was unusually low in the control group, whereas the personnel and patient groups showed normal levels of chromosome aberrations which did not differ from previously studied control groups. There was no statistical difference in the frequency of chromosome aberrations or DNA breaks in the patient group after, as compared to before, operation. Smokers were found to have a significantly increased frequency of chromosome gaps compared to nonsmokers, but there was no indication that this difference was related to anaesthetic exposure. The data presented give no indications of genotoxic effects in vivo of inhalation anaesthetics by either occupational exposure to waste anaesthetic gases, or anaesthesia during operation. On the other hand, our present data do not contradict previous data indicating that hospital personnel, irrespective of exposure to inhalation anaesthetics, may have a small average increase of chromosome abnormalities.

Adult↗
PubMed1982

Sister chromatid exchange in human populations: the effect of smoking, drug treatment, and occupational exposure.

Increased rate of sister chromatid exchange (SCE) in peripheral lymphocytes has been observed in smokers as compared to nonsmokers and in patients receiving certain cytostatic drugs. The increased SCE frequency in smokers was shown to depend on the number of cigarettes smoked per day, as well as on the duration of smoking. DNA cross-links caused by photochemotherapy against psoriasis, 8-methoxypsoralen plus UVA irradiation (PUVA), as well as by the anti-cancer chemotherapeutic agent CCNU, were shown to be more effective at inducing SCE's than other types of DNA damage caused by these treatments. These observations suggest that SCE analysis may be used as an indicator of genotoxic exposure in vivo, provided that the various types of DNA damage caused by genotoxic agents and the dose, as well as the time of exposure in relation to the time of sampling, are considered.

Crossing Over, Genetic↗
PubMed1982

DNA repair synthesis in subpopulations of human lymphocytes.

Human peripheral blood lymphocytes enriched in T or B cells were exposed to ultraviolet irradiation, nitrogen mustard or methylmethane sulphonate and investigated regarding their capacity for DNA repair synthesis. The DNA repair synthesis, measured as [3H] thymidine incorporated, was determined by autoradiography as unscheduled DNA synthesis (UDS). No systematic difference could be found in the capacity for UDS between the T- and B-cell-enriched fractions. A larger individual variation in UDS was found in the B-cell- compared to the T-cell-enriched lymphocytes.

B-Lymphocytes↗
PubMed1982

Smoking and sister chromatid exchange.

Smokers were shown to have significantly higher SCE levels in peripheral lymphocytes than non-smokers. The increase of SCE was found to depend on the cigarette consumption, and to be significantly higher in subjects with a long than with a short history of smoking. Analysis of the frequency distribution of individual SCE levels and of SCE numbers in single cells gave no indication of subgroups of individuals of subpopulations of lymphocytes with an increased SCE response to smoking. Cells from smokers cultivated in plasma from non-smokers retained a high SCE level, and cells from non-smokers cultivated in plasma from smokers no increase of SCE, indicating that the increase of SCE caused by smoking is due to some type of (long-lived) cellular damage rather than to serum factors. The plasma levels of the primary nicotine metabolite cotinine were found to be increased in heavy smokers as compared to light smokers, and showed an excellent correlation with the cotinine levels in the amniotic fluid in pregnant female smokers. No correlation was found between the individual SCE and cotinine levels in smokers, which indicates that the degree of exposure to SCE-inducing genotoxic agents in the cigarette smoke is not related to plasma cotinine levels in any simple way. The induction of DNA strand breaks and SCE by two intermediary benzo(a)pyrene (BP) metabolites was studied in human lymphocytes in vitro. Both 9-OH-BP and BP-7,8-dihydrodiol were found to induce DNA breaks, but only the latter compound induced SCE. The SCE-inducing effect of BP-7,8-dihydrodiol was observed at a very low concentration (0.01 microM), which indicates a possible role for this BP derivative in the smoking-induced increase of SCE in vivo.

Benzopyrenes↗
PubMed1981

Relation between sister chromatid exchange, cell proliferation and proportion of B and T cells in human lymphocyte cultures.

Human B and T lymphocytes differ in the rate of cell proliferation and frequency of sister chromatid exchange (SCE) when cultured separately in short-term cultures. This difference could theoretically be responsible for part of the variation in the SCE-frequency previously observed among healthy subjects since there is individual variation in the proportion of B and T cells in the peripheral blood. We have therefore studied cell proliferation and SCE-frequency in conventional short-term cultures of lymphocytes from 28 healthy subjects with different proportions of B and T cells. The percentage of B or T lymphocytes did not correlate with the SCE-frequency, nor with the rate of cell proliferation in culture. However, a significantly higher SCE-frequency was found in slowly proliferating cultures than in cultures with a high rate of turn over. Thus, the rate of cell proliferation appears to be an important determinant of the SCE-frequency in conventional lymphocyte cultures. Although the data do not exclude attribution of the difference in SCE- frequency between rapidly and slowly growing cultures to differences in subpopulations of lymphocytes, it appears less likely that B and T cells constitute these tentative subpopulations.

B-Lymphocytes↗
PubMed1981

Gluconobacters from honey bees.

Fifty-six Gluconobacter strains and one Acetobacter strain were isolated from honey bees and their environment in three different regions in Belgium and identified phenotypically. Polyacrylamide gel electrophoresis of the soluble cell proteins showed that two different types exist within the Gluconobacter isolates: strains from type A were found in samples of the three regions, whereas strains from type B were only isolated in two of the three regions. Both types could occur in bees from the same region, from several hives of one bee keeper and from one hive. Strains from type A were almost identical with collection strain G. oxydans subsp. suboxydans NCIB 9018, whereas strains from type B constituted a new protein electrophoretic type within the genus Gluconobacter. Although Gluconobacter is apparently associated with honey bees, it is not known whether it is important or required for the bees or any hive product.

Animals↗