RESUMO
3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a by-product of wood pulp manufacture and a contaminant of chlorinated drinking water, was investigated for potential teratogenicity using the micromass in vitro test system. Twelve-day rat embryo midbrain (central nervous system, CNS) and limb bud (LB) cells were exposed to MX at concentrations of 1, 2, 5, or 10 microg/ml in the culture medium with or without S9 mix. Under the experimental conditions, the amount of MX rapidly declined in the culture medium with a half-life of 56 min. Nevertheless, differentiation of CNS and LB cells was significantly inhibited at concentrations of 2 microg/ml or more, when the cells were exposed to MX in the absence of S9 mix. The estimated IC50 was approximately 3 microg/ml for both CNS and LB cell cultures. On the other hand, exposure of CNS and LB cells to MX along with S9 mix did not reduce the number of differentiated foci at any concentrations tested. These results suggest that MX may be a potential direct-acting in vitro teratogen.
Assuntos
Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Furanos/toxicidade , Mutagênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Sistema Nervoso Central/embriologia , Relação Dose-Resposta a Droga , Extremidades/embriologia , Técnicas In Vitro , Ratos , Abastecimento de ÁguaRESUMO
A 74-year-old woman with a right ovarian tumor had a high level of the serum tumor marker alpha-fetoprotein (AFP). After combination chemotherapy, the serum AFP level decreased significantly. Histopathologic study of surgically excised tumor tissue revealed a serous papillary cystadenocarcinoma. By the indirect immunoperoxidase technique, the AFP was stained in the cytoplasm of the differentiated tumor cells, showing papillary or tubular structures. Serial sections showed that the cells containing PAS-positive substances did not correspond to those producing AFP.
Assuntos
Cistadenocarcinoma/metabolismo , Neoplasias Ovarianas/metabolismo , alfa-Fetoproteínas/biossíntese , Idoso , Antígeno Carcinoembrionário/análise , Cistadenocarcinoma/sangue , Cistadenocarcinoma/patologia , Feminino , Histocitoquímica , Humanos , Histerectomia , Técnicas Imunoenzimáticas , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Radioimunoensaio , Coloração e Rotulagem , alfa-Fetoproteínas/análiseRESUMO
Effects of lisuride, a central dopaminergic agonist of the ergot type, on the biosynthesis, release and metabolism of dopamine at the dopaminergic nerve terminals of the rat brain were studied under several experimental conditions. 1) In the rat whose impulse flow of dopamine neurons and the activity of aromatic amino acid decarboxylase were inhibited by the pretreatment with gamma-butyrolactone and with 3-hydroxybenzylhydrazine (NDS 1015), respectively, DOPA formation in the neostriatum and limbic forebrain were decreased significantly by the s.c. administration of lisuride at the dosage known to be ineffective on the postsynaptic dopamine receptor. 2) When it was measured by the accumulation of 3-methoxytyramine in the neostriatum and limbic forebrain of pargyline (MAO inhibitor)-pretreated rats, lisuride at the low dosage caused the inhibition of not only the spontaneous release of dopamine from the nerve terminal to the synaptic cleft, but also the release induced with methamphetamine. 3) In the rat whose dopamine biosynthesis was inhibited with alpha-methyl-p-tyrosine, lisuride caused the suppression of dopamine metabolism, resulting in significant increases of dopamine histofluorescence in the nucleus caudatus, olfactory tubercle and median eminence. As to the effect on dopamine histofluorescence, apomorphine at 1 mg/kg was equipotent to lisuride at 50 micrograms/kg. It was concluded from these results that lisuride administered at low dosage interacts preferentially with the presynaptic dopamine receptor, hereby causing the suppressive effects on the tyrosine hydroxylase reaction and the dopamine release mechanism in the dopamine nerve terminals of the brain.