Effects of chlorinated dibenzofuran and dioxin on concentration and pattern of chlorobiphenyls and activity of benzo(a)pyrene hydroxylation in mice

To experimentally assess whether one of the characteristic polychlorinated biphenyl (PCB) patterns in tissues of Yusho patients is caused by the treatment of polychlorinated dibenzofurans (PCDFs), mice were treated i.p. for 6 consecutive days with Kanechlor (KC)-400 (1.2 mg/kg) alone or KC-400 (1.2 mg/lg) plus 2,3,4,7,8-pentachlorodibenzofuran (Pen-CDF, 0.3~30 μg/kg) or KC-400 (1.2 mg/kg) plus 2,3,7,8-tetrachlorodibenzo-p-dioxin (TC-DD, o.3~30 μg/kg), and 30 days after the last treatment, the animals were killed. Hepatic aryl hydrocarbon hydroxylase (AHH), one of the representative drug metabolising enzymes, activity and concentrations of total PCBs, 2,4,5,3',4'-pentachlorobiphenyl (2,4,5,3',4'-Pen-CB) and 2,4,5,2',4',5'-hexachlorobiphenyl (2,4,5,2',4',5,-HCB) in the liver, adipose tissue and lungs were determined. A ratio og 2,4,5,3',4'-PenCB to 2,4,5,2',4',5'-HCB in concentration was calculated in the tissues, as this PCB ratio in Yusho patients is characteristically low as compared with that in normal persons. Hepatic AHH activity increased in parallel with the increase in doses of PenCDF or TCDD, and the ratio in every tissue generally showed an increasing tendency in rough proportion to the increase in the enzyme activity, so we failed to experimentally reproduce one of the characteristic PCB patterns of Yusho patients. The result, however, may be explained by genetic polymorphisms of drug metabolism. The time at which samples are analyzed for PCBs after the exposure to PenCDF or TCDD may be also an important factor to detect some peculiar PCB patterns. We also observed decreased concentration of total PCBs in the liver and increased concentration of those in the lungs of mice treated with KC-400 plus PenCDF or KC-400 plus TCDD compared with the concentrations in both organs of mice treated with KC-400 alone. At the present time, biological and/or toxicological significance of the observation is unclear.