[Action of ionizing radiations and sulfhydryl radioprotective substances on the synthesis of nuclei acids].
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Biomedical subjects
Publications and source records attributed to L Baugnet-Mahieu.
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The activation of the p34cdc2/cyclin B complex is responsible for driving the cell cycle from the G2- to the M-phase. To investigate the effects of irradiation on the activity of the p34cdc2/cyclin B complex in preimplantation embryos, we irradiated one-cell mouse embryos with 2.5 Gy of X-rays at the early pronuclear stage, and measured the fluctuations of histone H1 kinase activity (a biochemical indicator of the kinase activity of the p34cdc2) at different times during the radiation-induced G2-arrest. BALB/c embryos were chosen for these experiments, since earlier results obtained in our laboratory had shown that such a treatment induces a G2-arrest of about 20 hours in more than 90% of the embryos. Our data showed that histone H1 kinase activity of irradiated embryos remained at a very low level during the period of G2-arrest. The level of activity found during late division of the G2-arrested embryos was also significantly lower in comparison with that of control embryos or irradiated embryos dividing without delay. All together, our results suggest that a) low levels of histone H1 kinase activity are sufficient for the division of one-cell embryos, b) there could be a link between the levels of histone H1 kinase activity in mitosis and the health status of the embryo.
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Epidermal growth factor receptors (EGF-R) have been measured in human tumors of the Central Nervous System (CNS) by 125I EGF ligand binding. High affinity receptors (Ka congruent to 1 x 10(9) M-1) were detected in nearly all individual specimens of meningiomas and tumors of glial origin (astrocytomas, glioblastomas). The phosphotyrosine kinase activity associated with the EGF-R was evaluated by measuring the incorporation of gamma 32P-ATP, after immunoprecipitation of the receptor with the monoclonal antibody EGFRI. A good relationship was observed between the EGF-binding capacity and the autophosphorylation of the receptor, indicating that in most cases functional molecules of EGF-R were expressed on the tumor membranes. In the group of meningiomas, no relationship could be established between the EGF-R level and the histopathology of the tumors. Astrocytomas exemplify a progression of malignancy, from benign (low grade astrocytomas) towards an increased malignant phenotype (glioblastomas). In this group, our observations indicate a positive relationship between the EGF-R level and phosphokinase activity and the degree of malignancy.
Saturable, high affinity binding sites for 3,5,3' triiodothyronine (T3) were identified in nuclei isolated from human tumors of various origins (breast cancers, other epitheliomas, sarcomas, tumors of the central nervous system). Nuclear T3 receptors were present in all samples of primary breast cancer (n = 93; average Cmax = 215 fmol/mg DNA) and in metastatic tissues originating from breast tumors. A significantly lower T3 binding capacity was found in non-tumor tissues, obtained from breast sites distal to the tumor (n = 30; average Cmax = 133 fmol/mg DNA; paired t-test: p less than 0.01). Specific nuclear T3 receptors were also present in other epitheliomas (n = 8; average Cmax = 432 fmol/mg DNA), sarcomas (n = 4; average Cmax = 297 fmol/mg DNA) and cerebral tumors (n = 13; average Cmax = 364 fmol/mg DNA. In 93 cases of breast cancer, a negative relationship was found between the nuclear T3 receptor level and the involvement of axillary lymph nodes (Pearson chi square value: p = 0.017). Except a possible relationship between the T3 receptor and the progesterone receptor concentrations, no significant correlation was observed between the nuclear T3 binding capacity in breast cancer samples and other clinical and biochemical parameters: age, tumour stage, histopathological grade, serum concentrations of thyroid hormones, TSH, CEA (carcinoembryonic antigen) and prolactin, cytoplasmic estrogen receptors. The presence of high affinity T3-binding sites in human tumor nuclei indicates that the thyroid hormones may play a role, at the cellular level, on the development of certain human cancers.