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M L Larramendy

Publications and source records attributed to M L Larramendy.

61 records · Page 4Linked to original sources

Mitomycin C-induced damage and repair in human and pig lymphocytes.

Human and pig lymphocytes were used to compare the chromosomal sensitivity to MMC and the efficiency of repair of MMC-induced DNA adducts. No significant interspecies differences were found. The results obtained show that SCE frequencies are linearly correlated with MMC doses. During the G0 period there are indications that lymphocytes may half-repair the DNA-interstrand crosslinks transforming bi- into mono-adducts. SCEs induced by MMC decrease to near control levels in the second cell cycle. Therefore, most MMC lesions responsible for SCEs should be repaired between the moment in the first S phase in which they induce the exchanges and the onset of the second S period.

Animals↗

The effects of incorporated tritium and bromodeoxyuridine on the frequency of sister chromatid exchanges.

Cells in third mitosis treated during the first cell cycle with 3H-TdR and during the next two cycles with BrdU (without 3H-TdR) show a typical pattern of chromosome differentiation which allows identification of sister chromatid exchanges occurring during the first (SCE1), second (SCE2) and third cycles (SCE3). Chromosomes labeled only with 3H-TdR had the most SCEs; those labeled only with BrdU, the second highest number; and those labeled with 3H-TdR plus BrdU, the fewest. Since BrdU and 3H-TdR are well known inducers of SCEs, the relatively low frequency of exchanges produced by the combined action of these two compounds is paradoxical. It is assumed that SCEs are generated by the abnormal recombination of double-strand DNA breaks occurring at the junctions between completely and partially duplicated replicon clusters. Thus, agents that induce absolute blocks to DNA fork displacement will favor the appearance of SCEs because double-strand breaks have more time to occur at junctions. Conversely, agents that inhibit the initiation of replication will decrease the probability of SCEs. Ionizing radiation delays the onset of cluster replication. Therefore, in 3H-TdR plus BrdU-substituted chromosomes the radiation from tritium may inhibit the appearance of BrdU-induced SCEs. Since the inhibition does not exist in chromosomes substituted only with BrdU, the frequency of SCEs in these elements is higher than in double-substituted chromosomes. During the first cell cycle the onset of cluster replication is normal. However, the incorporation of 3H-TdR in the replication fork may enhance the appearance of double-strand breaks, thus inducing a high frequency of SCEs.

Autoradiography↗

12-O-tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in Syrian and Chinese hamster cells.

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10 microgram/ml medium) and the number of cell divisions post treatment TPA (0.01-2 microgram/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-inactivated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation.

Animals↗

Effect of caffeine on the frequency of chromosome aberrations induced in vivo by triethylenemelamine (TEM) and adriamycin (ADR) in mice.

The effect of caffeine on the chromosomal aberrations induced in vivo by TEM and ADR was studied. BALB/c mice were treated intraperitoneally according to the schedule summarized in Table 1. Animals injected only with caffeine exhibited a significant increase in the frequency of gaps with the doses of 100 and 150 mg/kg and in the frequency of breaks with all the doses given. Treatments with TEM induced a significant increment of gaps, breaks and chromatid exchanges. ADR increased the frequency of gaps and breaks and induced centric fusions. Combined treatments with TEM plus caffeine evidenced the potentiating ability of the latter drug. Conversely, in mice injected with ADR and caffeine, only the frequency of centric fusions was increased. These results could be explained by assuming that: (1) the primary lesions induced by ADR are not repaired by post-replication mechanisms; (2) the binding of ADR to the DNA molecule inhibits the unscheduled DNA synthesis necessary to perform the reparation of damaged segments. On the other hand, the increased frequency of biarmed chromosomes in ADR-caffeine treatments probably results from the induction of chromosomal stickiness of the heterochromatin regions.

Animals↗

In vivo dose-response relationship in bone-marrow cells of mice treated with adriamycin.

In bone-marrow cells of mice treated with a single dose of adriamycin and killed 6 h later, only chromatid-type aberrations were found. Animals studied 12 h after adriamycin injection showed chromatid- and chromosome-type aberrations, including Robertsonian centric fusions. The frequency of chromatid-type aberrations exhibited a direct-correlation with the dose in mice treated for 6 but not for 12 h. On the other hand, chromosome-type aberrations detected 12 h after injection were directly correlated with the dose of adriamycin. The induction in vivo of chromosome-type aberrations in mice studied 12 h after treatment suggests the existence of bone-marrow cell populations able to carry out 2 mitoses in this time lapse. The induction of Robertsonian fusions can be explained by the preferential induction of chromosomal lesions in pericentromeric heterochromatin followed by reunion of damaged segments of 2 chromosomes. Consequently, the metacentric-like chromosomes induced by adriamycin arise either from translocations involving entire chromosomes arms or from aberrations of the exchange type between 2 short arms of acrocentric chromosomes.

Animals↗

Genotoxic and aneugenic properties of an imidazole derivative.

To contribute to a more accurate characterization of the mutagenic and aneugenic effects of thiabendazole (TBZ), a widely used antiparasitic and food preservative drug, the induction of sister chromatid exchanges (SCEs) and mitotic spindle anomalies as cytogenetic end-points were investigated. Studies were carried out in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. A significant dose-dependent increase in SCE frequency was observed in CHO cells with S9-Mix (P < 0.01) in the 50-100 microg ml(-1) dose-range, while in the absence of S9-Mix, an enhancement of the SCE frequency was exhibited at the highest dose (P < 0.01). In CHO-K1 cells a significant increase in mitotic spindle anomalies (P < 0.01) was observed with the highest concentration assayed reflecting the specific effect of TBZ formulation at the microtubule level. Cell proliferation kinetics (CPK) were not modified by the addition of this pharmaceutical product. In human lymphocyte cultures, exposure to 100 microg ml(-1) TBZ formulation resulted in a significant decrease of the mitotic index (MI) (P < 0.003) and changes in the replication index (RI) (P < 0.05).

Aneugens↗