Clastogenic effects induced in mice and rats by 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene, a phenobarbital-like enzyme inducer and liver tumour promoter. 1988

A M Rossi, and L Zaccaro, and F Rosselli, and C Quattrone
Dipartimento di Scienze dell'Ambiente e del Territorio, Localita, La Torretta, S. Piero a Grado, Italy.

The clastogenic activity of 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP), a phenobarbital-like enzyme inducer and liver tumour promoter, was studied in mammalian cells exposed in vivo and in vitro. The effects of an oral treatment with 3 mg/kg body weight of TCPOBOP were scored in the bone marrow cells and in the liver cells of B6C3F1 hybrid mice. A relevant increase in the frequency of chromosomal aberrations was observed in both cell types. A co-administration of TCPOBOP and carbon tetrachloride (the latter given to stimulate liver cell divisions) produced similar effects to those induced by TCPOBOP alone. Several i.p. doses (1, 3, 10, 30 or 100 mg/kg body weight) were administered to Swiss-albino mice and to Sprague-Dawley rats. In bone marrow cells, a remarkable concordance between the two species was observed: at any dose higher than 3 mg/kg body weight the increase in frequency of chromosomal aberrations was more than three times the control level, with a slight decrease at the highest dose. A dose of 300 mg/kg body weight was lethal. Doses of 3 or 30 mg/kg body weight were also administered i.p. to partially hepatectomized rats and the effects on metaphase chromosomes were detected in the liver cells. Besides an increase in structural chromosomal aberration frequency, TCPOBOP induced high percentages of hypodiploid and hyperdiploid-hypotetraploid liver cells. Since no changes in euploidy were observed in the bone marrow cells, this effect seems to be tissue specific. The clastogenic activity of TCPOBOP was also confirmed in vitro by a rat lymphocyte assay without addition of any exogenous metabolic activation.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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