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.

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.