Short-term assays to predict carcinogenicity. Assays for genetic changes in mammalian cells.
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Animals↗
Biomedical subjects
B Lambert
Publications and source records attributed to B Lambert.
Short-term assays to predict carcinogenicity. Assays for germ-cell mutations in mammals.
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Animals↗
Chromosome damage and second malignancy in patients treated with melphalan.
Cytogenetic studies were carried out on peripheral lymphocytes from cancer patients at different times after therapy with melphalan. The frequency of sister chromatid exchange (SCE) was increased markedly shortly after treatment, and then declined to near pretreatment levels over a four-week period. In-vitro studies showed that the SCE frequency induced by melphalan is reduced slowly in resting G0 lymphocytes and considerably faster in mitogen-stimulated G1 cells. The results demonstrate that measurement of SCE is useful for the study of newly-induced chromosome damage in melphalan-treated cells, but is less suitable for the detection of persistent, cytogenetic alterations long after therapy. The frequency of chromosomal aberrations in a cohort of 50 patients with ovarian carcinoma was increased for up to ten years after melphalan therapy. The predominant aberrations were chromosomal translocations, marker chromosomes and cells with multiple, complex rearrangements. The frequency distribution of chromosomes involved in aberrations was studied in cells from some of the patients. An overrepresentation of chromosomes 8 and 9 was found in these cells, whereas the X chromosome was overrepresented in cells from control subjects. An increased frequency of chromosomal rearrangements was found in long-term cultures of T-lymphocytes from three of the patients, indicating that these aberrations are compatible with cell survival and proliferation. Seven patients in the cohort developed a second, primary tumour during the observation time. The frequencies and types of aberrations in these patients were similar to those of the other patients in the cohort.
Carcinoma↗
Tetradecanoyl phorbol-13-acetate counteracts the responsiveness of cultured thyroid cells to thyrotropin.
We have studied the effects of TPA on the metabolism of porcine thyroid cells cultured for 1-4 days in the absence (control cells) and in the presence of 0.1 mU/ml TSH (TSH cells). The phospholipid turnover, evaluated after a 2 hr incorporation of 32P-phosphate into phospholipids, is markedly modified by the presence of TPA (1.5 microM, 2 hr) in the incubation medium of control and TSH treated cells. The total incorporation is 3-4 times higher than untreated cells, the labelling of phosphatidylinositol (PI) is slightly decreased or unchanged whereas that of phosphatidylcholine (PC) is strongly increased. The increased labelling of PI, promoted by an acute TSH treatment is counteracted by TPA. This TPA effect is not observed when prelabelled cells are challenged for 5 min with the drug. A similar effect is observed when 10 nM TPA is added in the culture medium for 20 hr. The addition of TPA does not affect significantly the protein iodine content in 3 or 4 days control cells incubated for 45 min or 2 hr with 125I-iodine, but dramatically decreases the very high iodination rate of TSH cells. We have tested the TPA effect on the cyclic AMP accumulation for the last 5 min of a 2 hr incubation. TPA inhibits by about 50-80% the stimulation evoked by TSH and only by 10% that evoked by forskolin (0.1 mM). These results suggest a possible link between the PC turnover and the adenylate cyclase responsiveness to TSH and the iodination rate.
Adenylyl Cyclases↗
Comparative effects of cholera and Bordetella pertussis toxins on cyclic AMP and GTP levels and on lipolysis in rat adipocytes incubated in vitro.
The respective effects of cholera and Bordetella pertussis toxins were studied in time and concentration dependent experiments, following glycerol and fatty acid release, GTP and cAMP levels. Cholera toxin, after a lag time of 30 min, stimulated linearly GTP and cAMP accumulation and lipolysis (maximal effect: 2-fold increase at 5 micrograms/ml). Pertussis toxin presented a biphasic effect both in time and concentration dependent studies. Up to a maximum reached after 2 h with 1.4 units LPF/ml the stimulation affected GTP (3 fold) and cAMP (7 fold) levels, glycerol and fatty acid release (15 fold). Beyond this, an inhibition occurred, yielding a decrease towards basal values of GTP and cAMP content whereas the glycerol and fatty acid release was stopped. These results, which are the first reporting the fluctuation of the GTP content of intact cells challenged with bacterial toxins, show a close relationship between GTP and cyclic AMP levels and lipolytic activity.
Adipose Tissue↗
Erratum: Luminescence processes at chromium in GaAs
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Journal Article↗
Trichomonas vaginalis infestation in sexually abused girls.
We report infection with Trichomonas vaginalis in four sexually abused girls; two of these patients are unique in that they were premenarchal. We discuss the clinical features in premenarchal and postmenarchal children and relate infection to the likelihood of prior sexual abuse.
Child↗
Visualisation of a thyroglossal duct.
After ablation of an autonomously functioning thyroid nodule resulting from an adenoma, a previously suppressed scintigraphic image of a thyroglossal duct was visualised.
Adenoma↗
Induction and persistence of SCE-inducing damage in human lymphocytes exposed to vinyl acetate and acetaldehyde in vitro.
The frequency of sister-chromatid exchange (SCE) was studied in cultures of human lymphocytes exposed to vinyl acetate (VA) or acetaldehyde (AA) for various time periods and in different phases of the cell cycle. Equimolar concentrations (0.1-2.4 mM) of VA and AA were found to induce very similar, dose-dependent increases of SCE. The SCE frequency in cells treated with VA was found to increase linearly with exposure times up to 24 h. Cells exposed to VA or AA in the late G1-phase of the cell cycle showed a 2-fold higher SCE frequency than cells exposed in early G1. Cultures treated with VA in the first G1-phase showed a significant increase of SCE during 3 subsequent cell cycles. These results indicate that (1) AA is likely to be responsible for the SCE induction observed in VA-treated cells, (2) the SCE-inducing activity of AA persists for several cell cycles in vitro, and (3) removal of SCE-inducing AA-damage occurs during G1. Taken together, the data suggest that AA has a slow turn-over in human lymphocytes in vitro, and may accumulate in the cells, possibly by forming reversible Schiff bases, and when released gives rise to SCE-inducing DNA cross-links.
Acetaldehyde↗
DNA cross-links in human leucocytes treated with vinyl acetate and acetaldehyde in vitro.
Human leucocytes were incubated in the presence of vinyl acetate or acetaldehyde (10-20 mM) for 4 h at 37 degrees C in vitro. DNA damage was analysed by alkaline elution. None of the compounds induced a detectable increase in the frequency of DNA strand breaks. Cells exposed to 5 Gy of X-ray immediately after treatment and before alkaline elution showed a clear, dose-dependent retardation of the elution rate in comparison with X-irradiated control cells. These results demonstrate that both vinyl acetate and acetaldehyde induce DNA cross-links in human cells.
Acetaldehyde↗
Chronic and acute effects of forskolin on isolated thyroid cell metabolism.
The chronic treatment (2 days or more) of cultured thyroid cells with 1-10 microM forskolin (forskolin-treated cells) sensitizes the response of adenylate cyclase to further acute stimulation by 100 microM forskolin or 10 mU/ml thyrotropin (TSH). This positive regulation, similar to that produced by 0.1 mU/ml TSH (TSH-treated cells), is obtained between 2 and 3 days of culture. The acute response to TSH or forskolin of cells treated for 4 days with forskolin increases with the concentration of forskolin present during the chronic treatment. This result is different from that obtained after a chronic treatment with TSH which induces refractoriness beyond 0.1 mU/ml. These cells are then desensitized to TSH but not to forskolin. When both agonists are mixed together, their acute effect is additive on control, TSH- and forskolin-treated cells. The chronic treatment of cultured thyroid cells with 1-10 microM forskolin produces, just like 0.1 mU/ml TSH, a chronic phospholipid effect characterized by enhanced incorporation of 32Pi into phosphatidylinositol (PI) and phosphatidic acid. The acute challenge of these cells with 100 microM forskolin evokes a reverse phospholipid effect, i.e. a decreased incorporation of 32Pi into PI. The acute stimulation of TSH-treated cells with TSH produces a reverse phospholipid effect whereas the acute stimulation of forskolin-treated cells with TSH gives a normal phospholipid effect as it does on control cells. These results show that the observed effects of TSH on cAMP accumulation and phospholipid turnover are not independent and are regulated in an inverse reciprocal pattern.
Animals↗
Colpohistologic correlations. A computerized study.
Data from 300 colposcopic cases were computerized to study the correlations between the colposcopic observations and the histologic and other data. Colposcopy was shown to be most useful in women under 35 years of age. Use of oral contraceptives (the Pill) seemed to relate to a higher level of successful colposcopic visualization and may even prevent the need for conization, based on a higher incidence of negative endocervical curettages. Although 14.5% of the cases were colposcopically undergraded and 17% overgraded when compared to the histopathology, the histologic predictability of the colposcopic observation of white epithelium and vascular changes (punctation and mosaicism) was excellent. Colposcopy remains an essential technique in the appraisal and management of cervical intraepithelial neoplasia.
Adult↗
Unsuccessful lung scan due to major right-to-left shunt through a sinus venosus septal defect.
In a patient with a prior history of cerebral abscess and cerebral ischemia, an unsuccessful perfusion lung scan led to a radionuclide angiocardiogram using an arm vein injection. This showed a total right-to-left (R-L) shunt from the superior vena cava (SVC) to the left atrium. Repeat radionuclide study, through a leg vein, demonstrated a moderate R-L shunt and an interpretable lung scan could be obtained. Catheterization and contrast cineangiogram did not provide the exact diagnosis, the preoperative conclusion being anomalous drainage of the SVC into the left atrium, with atrial septal defect (ASD) and partial anomalous pulmonary venous connection to the SVC. The operative diagnosis was high atrial (sinus venosus) septal defect. This example of major but clinically unsuspected R-L shunt emphasizes the value of performing a perfusion lung scan, preferably in conjunction with radionuclide angiocardiography in patients with a prior history of unexplained cerebral abscess or systemic ischemia. Implications of the site of an ASD on quantitation of L-R shunts by radionuclide methods are also discussed.
Brain Abscess↗
Interactions between thyreostimulin and PAF-acether on thyroid cell metabolism.
1-O-Alkyl, 2-acetyl sn-glycerylphosphorylcholine (platelet activating factor (PAF)-acether) originally described as a platelet activating factor, is effective on various parameters in different cells. It seemed interesting to us to test it on porcine thyroid cells cultured for 1 to 5 days in the absence (control cells) or in the presence of 0.1 mU/ml thyreostimulin (TSH cells). At concentrations ranging from 0.5 to 2.5 microM, PAF-acether inhibited significantly the accumulation of cyclic AMP resulting from a 5 min incubation of the cells with TSH (40 mU/ml) or forskolin (0.1 mM). PAF-acether alone did not affect basal cyclic AMP accumulation. The maximal inhibition was obtained on a 3 day culture and amounted to 40-50%. The inhibition was transient and vanished after a 30 min incubation. The effects of PAF-acether (0.5 microM) on phospholipid metabolism depended closely upon the physiological state of the cells and upon the age of the culture. When PAF-acether was incubated for 2 h with [32P]phosphate, it mimicked the effects of TSH, i.e. it increased phosphatidylinositol (PI) labelling on 1 day control cells (expected effect) and decreased it with 1 day TSH cells (reverse effects). The PAF-acether effect was rapid in onset. After cell prelabelling for 2 h in the presence of TSH, PAF-acether added for 15 min completely counteracted the hormone effects on PI and phosphatidylcholine (PC) but increased the phosphatidic acid (PA) labelling. The effect of PAF- acether on PI labelling was partially antagonized by forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of mutation, electric membrane potential, and metabolic inhibitors on the accessibility of nucleic acids to ethidium bromide in Escherichia coli cells.
The uptake of ethidium bromide by Escherichia coli K 12 cells has been studied by using 14C-labeled ethidium and spectrofluorometry on three E. coli strains: the first one (AB1157) has an ethidium-resistant phenotype; the second one derives from the first one after a single mutation (at 10 min on the E. coli genetic map) and has an ethidium-sensitive (Ebs) phenotype; the third one is the acrA strain which appeared to have the same phenotype as the Ebs strain. When the cells are in exponential growth, no ethidium enters wild-type cells, and a very limited amount of ethidium enters Ebs and acrA cells. Massive quantities of ethidium enter AB1157, Ebs, and acrA cells treated by uncouplers and respiring Ebs cells treated by the membrane ATPase-inhibitor dicyclohexylcarbodiimide. A small amount of ethidium enters cells treated in M9 succinate medium by metabolic inhibitors such as KCN or cells starved with oxygen in the same M9 medium. The amount of ethidium and ethidium dimer retained at equilibrium by either type of cell, and by cells infected by T5 phage, as well as the kinetics of influx and efflux, has been measured under a variety of situations (membrane energized or not, and/or membrane ATPase inhibited or not). Furthermore, it was shown that ethidium binds to both RNA and DNA when it enters CCCP-treated wild-type E. coli cells, whereas it binds mainly to DNA when it enters Ebs and acrA cells in exponential growth. As it will be discussed, it is difficult to account for the EthBr uptake by invoking only membrane functions and active transport. Therefore, it is proposed that the variations of the nucleic acid accessibility in E. coli cells might play a role in the control of this uptake. Accordingly, in ethidium-sensitive cells, the mutation would have caused a significant part of the chromosomal DNA (10-20%) to become accessible to ethidium. Hansen [Hansen M. T. (1982) Mutat. Res. 106, 209-216], after a study of the photobinding of psoralen to nucleic acids in the acrA mutant, also suggested that DNA environment was modified in acrA cells.
Cell Membrane↗
A review of the International Symposium on Sister Chromatid Exchanges: twenty-five years of experimental research.
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Animals↗
Removal and persistence of SCE-inducing damage in human lymphocytes in vitro.
The SCE frequency was studied in PHA-stimulated human lymphocytes exposed to various SCE-inducing agents in different stages of the cell cycle. Melphalan, HN2, MMS, and UV light were found to induce a higher SCE frequency in late G1 (18-24 hr after PHA stimulation) than in early G1 (1-6 hr after PHA) or G0 (before PHA stimulation). In contrast, CCNU induced more SCEs in early G1 than in late G1, and the adriamycin-induced SCE frequency was about the same after treatment in early and late G1. These results suggest that SCE-inducing lesions are being removed at different rates in human G1 lymphocytes. The removal of SCE-inducing HN2 lesions was found to be about 10 times more rapid in late G1 than in early G1, indicating the activation of a cross-link repair mechanism prior to DNA replication in human lymphocytes. Cells treated with MMS in the second G1 (after cultivation for about 55 hr in the presence of PHA and BrdUrd) showed a higher SCE frequency than cells treated with the same dose of MMS in the first G1. This result indicates that some type of interaction occurs between MMS damage and BrdUrd lesions in the DNA during replication, which leads to an enhanced induction of SCE. Analysis of SCEs induced during the 2 first vs. the third cell cycle in third-generation metaphases showed that most of the SCE-inducing damage caused by treatment with HN2 and melphalan in G1 of the first cell cycle are removed before the S phase of the third cell cycle, whereas damage caused by MMS and adriamycin seem to be more persistent. These observations suggest that the rate by which different types of SCE-inducing damage are removed or modified in resting (G0) of PHA-stimulated human lymphocytes can have a great influence on the SCE frequency. This is of practical importance in studies using SCE analysis to evaluate human exposure to suspected genotoxic agents in the environment.
Alkylating Agents↗
Persistence of chromosome rearrangements in peripheral lymphocytes from patients treated with melphalan for ovarian carcinoma.
Chromosome aberrations were studied in peripheral lymphocytes from 50 patients treated with melphalan against ovarian carcinoma. The chromosome analyses were carried out 4-132 months (mean 57 months) after the end of melphalan therapy. Most of the patients were studied several times during four years. The mean frequency of cells with chromosome and chromatid aberrations was 5.4% in the patients and 2.3% in an untreated control group. The highest aberration frequency (average 18%) was found in a patient who later developed gastric carcinoma. The dominating types of aberrations in the patients were chromosome exchanges occurring as single marker chromosomes or as multiple chromosome rearrangements. These types of aberrations were found in only 0.3% of the control cells as compared to 3.8% of the patient cells. Patients with a high total dose of melphalan (above 420 mg) and a long duration of the therapy (average 22.5 months) had a higher frequency of cells with aberrations (6.3%) than patients with a lower total dose (below 420 mg) and a shorter therapy (12 months) (4.2%). No additive effect of radiation therapy was observed on the aberration frequency.
Adult↗