benzofurans and Immunologic-Deficiency-Syndromes

Clinical and experimental studies on respiratory involvement and alterations in immune status were carried out. Respiratory distress occurring in these patients has improved gradually for 14 years but still remains. Copious expectoration at an early stage of the disease may be related to the fact that a number of discrete polychlorinated biphenyls (PCBs) are distributed throughout the lung parenchyma. For accumulation in the bronchial mucosa, structural requirements and specific dose dependence of PCBs have been clearly shown; however, pathological and physiological studies have indicated that respiratory involvement in yusho is mainly small airway disease that may be caused by involvement of cellular component (Clara cells) in bronchioles and/or associated infection. Respiratory distress is often exacerbated by viral or bacterial infection. Changes in the immune status in PCB and polychlorinated dibenzofuran (PCDF) poisoning are as follows: IgA and IgM in the serum are decreased at an early stage of the disease and then return to normal; suppression of cellular immunity was reported in Taiwanese patients and some may remain in the later stages of the disease, as shown in our patients. PCDFs now appear to be the main causal agents in yusho. Rats given PCDFs showed necrosis of the Clara cells in bronchioles and marked thymus atrophy, while few such changes were noted in rats given PCBs. Therefore, further examination is needed for the difference of the toxic effects between two compounds.

Topics: Animals; Benzofurans; Dibenzofurans, Polychlorinated; Food Contamination; Humans; Immunologic Deficiency Syndromes; Japan; Lung; Oils; Oryza; Polychlorinated Biphenyls; Rats; Rats, Inbred Strains; Respiratory Tract Diseases; Thymus Gland

Male Sprague-Dawley rats were daily given orally for 22 days a regimen consisting of polychlorinated biphenyls (PCBs), 1 mg/day; polychlorinated quaterphenyls (PCQs), 1 mg/day; polychlorinated dibenzofurans (PCDFs), 10 micrograms/day; or a mixture of PCBs, PCQs and PCDFs (Mix-1, 1 mg + 1 mg + 10 micrograms/day). Female Cynomolgus monkeys were daily administered PCBs (5 mg), PCQs (5 mg) or a mixture (Mix-2) containing 5 mg PCBs + 20 micrograms PCDFs for 20 weeks. The PCBs, and PCDFs had the components of PCBs, PCQs and PCDFs similar to those contained in Japanese yusho oils, respectively. The PCB-treated rats and monkeys showed hepatic hypertrophy, immunosuppression and increased drug-metabolizing enzyme activities in hepatic microsomes, but were devoid of the dermal symptoms characteristic of yusho. PCQs caused an increase in drug-metabolizing enzyme activities in hepatic microsomes and immunosuppression in monkeys, but these effects were much smaller than those found with PCBs treatment. On the other hand, treatment with PCDF or Mix-1 or Mix-2 caused hypertrophy of the liver, immunosuppression, increase in drug-metabolizing enzyme activities of hepatic microsome to much greater extent than observed with PCBs, being more than 100 times as effective as PCBs. In addition PCDFs and the mixtures containing PCDFs caused weight loss and thymic atrophy. PCDFs and Mix-2-treated monkeys showed the dermal symptoms that are characteristic of yusho patients but were not observed in monkeys treated with PCBs and PCQs alone. These results suggest that PCDFs are the primary causative agent of yusho.

Topics: Animals; Benzofurans; Chlorobenzenes; Dibenzofurans, Polychlorinated; Enzyme Induction; Food Contamination; Humans; Immunologic Deficiency Syndromes; Macaca fascicularis; Male; Microsomes, Liver; Oils; Oryza; Polychlorinated Biphenyls; Rats; Rats, Inbred Strains; Species Specificity