Biomedical subjects

M E Gonsebatt

Publications and source records attributed to M E Gonsebatt.

32 records · Page 2Linked to original sources

PubMed1994

Mean dose to lymphocytes during radiotherapy treatments.

Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, we have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a 60Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model.

Chromosome Aberrations↗

PubMed1994

Altered urinary porphyrin excretion in a human population chronically exposed to arsenic in Mexico.

1. A detailed study of the urinary excretion pattern of porphyrins in humans chronically exposed to As via drinking water was performed using high performance liquid chromatography (HPLC) 2. Thirty-six individuals (15 men and 21 women) were selected from a town which had 0.400 mg L-1 of As in drinking water. The control group consisted of thirty-one individuals (13 men and 18 women) whose As concentration in drinking water was 0.020 mg L-1. 3. The major abnormalities in the urinary porphyrin excretion pattern observed in arsenic-exposed individuals were: (a) significant reductions in coproporphyrin III excretion resulting in decreases in the COPRO III/COPRO I ratio, and (b) significant increases in uroporphyrin excretion. Both alterations were responsible for the decrease in the COPRO/URO ratio. 4. No porphyrinogenic response was found in individuals with urinary As concentrations below 1,000 micrograms of As g-1 of creatinine. However, as arsenic concentrations exceeded this value, the excretion of porphyrins (except coproporphyrin III) increased proportionally. 5. The prevalence of clinical signs of arsenicism showed a direct relationship to both As concentration in urine and time-weighted exposure to As. A direct relationship between time-weighted exposure and alterations in urinary porphyrin excretion ratios was also observed. 6. The alterations found are compatible with a lower uroporphyrinogen decarboxylase activity in arsenic-exposed individuals. However, the similarities in the urinary porphyrin excretion pattern between As-exposed individuals and Dubin-Johnson syndrome patients suggest that impairments in the excretion of coproporphyrin isomers may also contribute to the pattern observed.

Adult↗

PubMed1993

Mitotic index and cell proliferation kinetics for identification of antineoplastic activity.

The mitotic index (MI) and cell proliferation kinetics (CPK) of human blood lymphocyte cultures were determined to evaluate the effects of six antineoplastic drugs with well known cytostatic activity: cisplatin, melphalan, bleomycin, methotrexate, 5-fluorouracil and 6-mercaptopurine. All six drugs showed a clear effect on the inhibition of MI. The first three drugs interact directly with DNA showing a dose-related retardation of CPK. Methotrexate, 5-fluorouracil and 6-mercaptopurine, which act on ribonucleotide biosynthesis, showed no significant effects on CPK. The results suggest that CPK and MI measurements are useful for the prescreening of drugs with potential cytostatic activity.

Adult↗

PubMed1993

The HPRT short-term assay in monitoring individuals exposed to genotoxic agents.

This paper reviews several monitoring studies where the short-term HPRT assay has been applied. The original method uses autoradiography to detect 3H-thymidine incorporation in variant cells that have undergone DNA synthesis; the bromodeoxyuridine modification employs this thymidine analog and fluorescence plus Giemsa staining. The studies discussed here were accomplished with either of these methods. methods. Exposures analyzed include radiation and chemotherapy as medical treatments and accidental exposures to radiation; these studies have been useful in the validation of the assay because radiation and anticancer drugs are well-known mutagens. Other potential mutagens such as environmental arsenic and a parasitic infection and praziquantel, used for its treatment, have also been monitored for hprt locus mutation. An overview of the results obtained with different agents and routes of exposure is presented here as well as some methodological aspects for the optimization of the assay for monitoring studies.

Autoradiography↗

PubMed1993

AS-101: a modulator of in vitro T-cell proliferation.

AS-101 is a tellurate compound originally designed as a drug with cytostatic activity. Nevertheless, in vivo it was found to be an immunomodulator agent due to a stimulation of cytokine production. Mitotic Index (MI) as an indicator of cytotoxicity and cell proliferation kinetics (CPK) in lymphocytes cultures are parameters used in the evaluation of the antineoplastic activity of drugs, such as mitomycin-C and cisplatin. For this reason, we evaluated the effects of AS-101 upon these two parameters. The results show that AS-101 produces an inhibition of MI in proliferating lymphocytes higher than the inhibition mediated by cisplatin. When CPK was evaluated, AS-101 induced a retardation not related with dose, while cisplatin produced a stepwise inhibition. This effect contrasts with the stimulation observed when AS-101 was added to non-proliferating lymphocytes which was measured as an increased [3H]thymidine incorporation in culture. The results confirm the mode of action of AS-101 as a real modulating agent of cell proliferation.

Adjuvants, Immunologic↗

PubMed1992

Effects of progesterone and estradiol on the proliferation of phytohemagglutinin-stimulated human lymphocytes.

In this paper we report on a study to elucidate whether the response of human lymphocytes to mitogenic stimulation was modified by physiological changes which occur during the menstrual cycle. Experiments with untreated cultures showed intra-individual variation to mitogen stimulation in female lymphocyte cultures, but a significant correlation between the menstrual cycle and the proliferation kinetics of lymphocytes was not found. Consequently, we performed experiments in which two of the hormones that regulate the menstrual cycle in women, estradiol and progesterone, were added to cultured human lymphocytes obtained from both men and women. The results indicate that both hormones at physiological concentrations have the capacity to modify the proliferation of PHA-stimulated human lymphocytes. Therefore, both hormones could play a role in the induction of the intra-individual variation observed in the untreated female cultures. However, in vivo other factors could also modify the proliferation kinetics of human lymphocytes preventing the demonstration of the effects of a single factor, such as the hormonal changes occurring during the menstrual cycle.

Adult↗

PubMed1992

Are mitotic index and lymphocyte proliferation kinetics reproducible endpoints in genetic toxicology testing?

Lymphocyte proliferation kinetics is an endpoint used in genetic toxicology which has recently been proposed as an alternative for the screening of new cytostatic drugs. Although great variability for this parameter has been reported, there are few reports about the intra- and inter-individual variation of the effects of chemicals on this endpoint. For this reason, experiments were conducted to evaluate the reproducibility of the effects of a well-known cytostatic, mitomycin C (MMC), on the proliferation of PHA-stimulated human lymphocytes, both over time and among samples from several donors. Although inter-individual variability was shown in both parameters in untreated and treated cultures, this variation was not significant. Intra-individual variation was significantly detected only in cultures treated with 0.1 microM MMC.

Adult↗

PubMed1992

Inorganic arsenic effects on human lymphocyte stimulation and proliferation.

Lymphocyte cultures from individuals exposed to high levels of hydroarsenicism showed a slower cell cycle kinetics than cultures from low-exposed individuals. Since this difference in proliferation could be due to chronic arsenic exposure, the in vitro effects of inorganic arsenic in human whole blood lymphocyte cultures were investigated. When lymphocytes were exposed to concentrations of arsenite and arsenate similar to those found in the blood of exposed subjects (10(-7), 10(-8) and 10(-9) M) during the last 24 h before harvesting, a dose-related inhibition of proliferation was observed. Cultures were also treated with 10(-9) M of arsenite and arsenate for 2, 6 and 24 h at the beginning of the cultures in the presence or absence of phytohemagglutinin (PHA). Inhibition of stimulation and proliferation was directly related to the length of treatment. The results show that, at the concentrations tested, arsenite and arsenate impair lymphocyte stimulation and proliferation and confirm the fact that chronic arsenic exposure can affect the proliferation of whole blood lymphocytes.

Adult↗

PubMed1991

Molecular differentiation of two different translocations producing two apparent Ph chromosomes in a patient with CML.

A case of chronic myelogenous leukemia (CML) is described whose leukemic cells appeared to contain two Philadelphia (Ph) chromosomes originating from different translocations involving the two chromosomes 22. The karyotype of the affected cells, established on two different occasions, was: 46,XY,t(9;22)(q34;q11),t(15;22)(p11;q11) with no normal chromosomes 22 and only one 9q+ in each of 115 marrow cells examined. The same findings were present in 50 peripheral blood cells cultured without phytohemagglutinin (PHA) stimulation. When stimulated with PHA, a normal male karyotype was present in the 11 cells examined. There were no additional chromosomal abnormalities and no indication of a blastic crisis after nearly 1 year following the original study. Analysis of the breakpoint cluster region (bcr) on chromosome 22 in the DNA of the affected cells (marrow) revealed evidence for one rearranged chromosome 22 and one normal chromosome 22, indicating that the t(15;22) was not due to the usual Ph translocation seen in CML. The results point to the crucial usefulness of molecular analysis in confirming cytogenetic results related to Ph translocations in CML.

Adult↗

PubMed1990

Human lymphocyte proliferation kinetics in Hanks' BSS supplemented with autologous plasma and in synthetic medium.

Human lymphocyte proliferation kinetics was studied in different culture conditions including synthetic medium, Hanks' BSS and Hanks' supplemented with autologous plasma at several culture times. Even though mitotic indices (MI) were low, lymphocytes were able to divide for a few cycles in BSS alone, with a cycling time of around 24 h. Similar cell proliferation patterns with similar MIs, replication indices and cell cycle times of approximately 12 h were obtained with RPMI 1640 and with autologous plasma-supplemented BSS, although lymphocytes exhibited a more uniform MI distribution curve in synthetic medium. The findings mentioned above suggest that Hanks' with autologous plasma may represent a suitable and inexpensive culture condition to avoid undesirable side effects related to synthetic media and heterologous sera, for diagnostics as well as research cytogenetics.

Acetates↗

PubMed1983

Sister-chromatid exchanges and cell kinetics in human and rabbit lymphocytes exposed in vivo and in vitro to 2-bromo-alpha-ergocryptine.

The possible mutagenic and DNA-synthesis inhibitory effects of 2-bromo-alpha-ergocryptine, a new semi-synthetic ergot alkaloid, was studied in human and rabbit lymphocytes exposed to it in vivo and in vitro. The analysis of SCE was mainly used to evaluate potential mutagenicity, and the mitotic and DNA-synthesis inhibition was explored by examining the proportions of first-, second- and third-division metaphases in the corresponding lymphocyte cultures. The results obtained show that 2-bromo-alpha-ergocryptine does not induce SCE in the cell systems tested, or structural chromosome aberrations in human lymphocytes in vivo. On the other hand, a marked mitotic inhibitory effect and associated cell kinetic changes could be clearly attributed to the drug, probably related to its cytotoxicity.

Animals↗

PubMed1981

Frequency and types of induced and spontaneous chromosome aberrations in relation to cell kinetics.

Induced and spontaneous structural chromosome aberrations (SCA) were studied in a child accidentally radiated with a high dose of 192Ir, and in three sibs with Fanconi's anemia, analyzing by separate first division metaphases (FDM) and second division metaphases (SDM). The results showed that the number of SCA, number of cells with aberrations, and SCA per cell were markedly higher in FDM in all patients. Furthermore, for some type of structural changes like dicentric chromosomes and chromatid interchanges, the differences were particularly striking. The importance of ascertaining FDM identified with proper techniques, for the study of the clastogenic effect of environmental agents and some aspects related to the differences in cytogenetic features found in diverse tissues in Fanconi's anemia are discussed.

Anemia, Aplastic↗

PubMedDate not supplied

Lymphocyte proliferation kinetics and genotoxic findings in a pilot study on individuals chronically exposed to arsenic in Mexico.

In the search for early biological markers to detect genetic damage, a pilot study on a hydroarsenicism-exposed group was designed. Blood and urine samples were taken from 11 individuals chronically exposed and from 13 individuals with lower exposure to the metal. Lymphocyte cultures for cytogenetic studies and HGPRT assay were done with coded peripheral blood samples, while arsenic levels and the "rec assay" in B. subtilis were determined in urine samples. The highly exposed group excreted greater amounts of As, nevertheless the rec assay showed negative results. An interesting finding is that the cell-cycle kinetics exhibited a significant difference between the groups studied, the average generation time (AGT) was longer in the highly exposed group. The percentages of chromosomal aberrations and the frequencies of sister-chromatid exchanges were similar in both populations, although complex aberrations were more frequent in the highly exposed group, which also showed a higher average variation frequency in the HGPRT assay, but the 2 latter observations were not statistically significant. The lag in lymphocyte proliferation could mean an impairment of the immune response due to arsenic exposure.

Adult↗

PubMedDate not supplied

Lymphocyte replicating ability in individuals exposed to arsenic via drinking water.

A human monitoring study was carried out to explore the effect on lymphocyte proliferation of chronic exposure to arsenic (As) via drinking water. Blood and urine samples were taken from volunteers from a town where levels of As in the drinking water averaged 412 micrograms/l, and from a matched group of individuals, with similar socioeconomic status, that drank water with As average levels of 37.2 micrograms/l. Exposure was assessed by questionnaires and by determining the levels of As in urine and water samples. The evaluation of the peripheral blood lymphocyte proliferation was done at different culture times using labelling (LI), mitotic (MI) and replication indexes (RI) as endpoints. No significant differences were seen for either LI or MI, except for MI in 72 h cultures and in LI in males and females with skin lesions vs. those without lesions. Significant differences in RI were seen for exposed females but not for males. Correlations between LI and MI showed that progression from the initial S-to M-phase is altered in exposed individuals. Arsenic exposure as well as lead and mercury affect cellular immune response, making the endpoints of cell proliferation variables of interest in population monitoring study design, since they might provide information in health impairment due to exposure, which is important in risk assessment.

Adult↗