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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
PubMed1984

Different SCE-inducing effects of HN2 and MMS in early and late G1 in human lymphocytes.

The induction of SCE was studied in PHA-stimulated human lymphocytes exposed to nitrogen mustard (HN2) or methyl methanesulfonate (MMS) for various time periods in the G1 phase. HN2 was found to induce about 10 times more SCE when cells were exposed in late G1 (24 h after PHA) as compared to early G1 (immediately after PHA). In contrast, only a small difference was observed between cells exposed to MMS in late or early G1. The results suggest that different types of SCE-inducing alkylating damage agents are removed at widely different rates in human G1-lymphocytes.

Cell Division↗
PubMed1984

Gossypol induces DNA strand breaks in human fibroblasts and sister chromatid exchanges in human lymphocytes in vitro.

The male contraceptive agent gossypol was found to induce a dose related increase of DNA strand breaks in human fibroblasts in vitro at concentrations of 5 to 40 micrograms/ml. The effect was reduced in the presence of 2% fetal calf serum. A weak but reproducible increase in the SCE frequency was found in human lymphocytes treated for 1 hour in serum-free medium with 0.04 to 4 micrograms/ml of gossypol.

Cells, Cultured↗
PubMed1983

Restoration by insulin of the responsiveness of stimulated adipocytes to adenosine.

The stimulation of adipocyte-cyclase by isoproterenol decreases its sensitivity to adenosine, with, as a consequence, a decrease in its antilipolytic effect. The presence of insulin under conditions where its action on the phosphodiesterase activity is impaired, restores the responsiveness of adenylate-cyclase and of lipolysis to adenosine.

Adenosine↗
PubMed1983

DNA repair replication, DNA breaks and sister-chromatid exchange in human cells treated with adriamycin in vitro.

The effects of adriamycin (AM) on DNA repair replication, the frequency of sister-chromatid exchange (SCE), the rate of cell proliferation and the frequency of DNA strand breaks were studied in human cells in vitro. No repair replication was observed in lymphocytes exposed to AM in concentrations up to 10(-3) moles/l. DNA repair replication induced by UV and alkylating agents was not affected by a concentration of AM that completely inhibited cell proliferation (10(-6) moles/l). Fibroblasts exposed to AM at 10(-4) moles/l in the presence of hydroxyurea showed an increase of strand breaks and cross-links in DNA. When AM was added to UV-irradiated fibroblasts, there was an increase of DNA strand breaks in addition to the breaks caused by UV alone. Similar effects were observed in lymphocytes. A dose-dependent increase of SCE was observed in lymphocytes exposed to low concentrations of AM (less than 10(-7) moles/l). At higher concentrations the increase of SCE levelled off, and cell proliferation became severely inhibited. There was no evidence of removal of SCE-inducing damage in cells exposed to AM during G0 or G1. The level of SCE induced in the third cell cycle after treatment with AM was not different from that induced during the first two cell cycles. These results suggest that the various genotoxic and cytotoxic effects of AM are caused by different types of cellular damage. Moreover, AM-induced DNA damage persists for several cell cycles in human cells in vitro and seems to be resistant to repair activity.

Cell Cycle↗
PubMed1983

Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irradiation.

To study the SCE-inducing effect of psoralen cross-links in the DNA of normal, human fibroblasts, cell cultures were exposed to PUVA (0.2-1 micrograms of 8-MOP per ml, followed by UVA irradiation at 0.04 J/cm2) and carefully washed to remove non-covalently bound psoralen. Some cell cultures were then given a second dose of UVA (1.1 J/cm2), either immediately after PUVA or 1-3 days later. By this type of treatment, cells with different proportions of DNA cross-links are obtained. The initial PUVA treatment will mainly give rise to psoralen monoadducts and only few cross-links in the DNA, and the second UVA irradiation will convert a number of the psoralen monoadducts into cross-links. SCE analysis was carried out on cells grown for 2 cell cycles in the presence of BrdUrd (10 mumoles/1). PUVA treatment alone did not induce an increase in the SCE frequency, whereas a clear increase of SCE was observed in cells treated with PUVA immediately followed by the second UVA dose. This PUVA + UVA-induced increase of SCE was also observed after incubation of the cells for 3 days at confluency, as well as when a period of 3 days at confluency was introduced between the PUVA exposure and the second irradiation with UVA. In contrast, the SCE frequency gradually returned to the normal level when PUVA + UVA-treated cells were allowed to proliferate for 1-2 days, or when a proliferation period of 2-4 days was introduced between the PUVA exposure and the second irradiation. Because the SCE frequency was not changed by the initial PUVA treatment but markedly increased by PUVA + UVA, it is concluded that psoralen cross-links are considerably more effective at inducing SCE than monoadducts. The results also indicate that SCE-inducing PUVA damage is removed very slowly if at all from the DNA of confluent cells. In contrast, repair functions that eliminate cross-links as well as monoadducts seem to become activated during cell proliferation.

Bromodeoxyuridine↗
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↗