Yoshito Masuda

Respiratory involvement in polychlorinated biphenyls poisoning

Abstract Clinical, laboratory, and pathological findings on respiratory involvement in polychlorinated biphenyl (PCB) poisoning were studied in 401 patients and their pathological changes were produced in rats given PCBs orally. Respiratory symptoms included expectoration in 40% of the 289 nonsmoking patients with PCB poisoning and mild wheezing in 2%. The incidence and severity of the respiratory symptoms correlated well with the concentration of PCBs in the blood and sputa. Chest roentgenographic findings, pulmonary function tests, and pathological findings revealed bronchiolitis in many, and pneumonia or atelectasis in about one-tenth of the patients with reticulo-linear shadows. Peribronchiolar changes may be primarily due to either PCB poisoning or associated infection. Respiratory distress was often exacerbated by viral or bacterial infection persisting for more than a half year in about half of the patients examined. The IgA and IgM levels in the serum decreased considerably within 2 years after the onset of the disease and definite decreases in IgA levels may correlate well with the bacterial infection. PCBs found in sputa may have been present in association with lipid in type II cells of the lung (or with excretion from bronchial cells) and may have been phagocytosed in alveolar macrophages and may change their phagocytic function.

Inducing Potency of Aryl Hydrocarbon Hydroxylase Activity in Human Lymphoblastoid Cells and Mice by Polychlorinated Dibenzofuran Congeners

Aryl hydrocarbon hydroxylase (AHH)-inducing potency of eight polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3,4,5-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxon (TCDD) in two inbred mouse strains (AHH responsive and nonresponsive mouse strains) and eight human lymphoblastoid cell lines (four males and four females) was investigated to evaluate their relative toxic potency. In AHH nonresponsive DBA mouse strain, only TCDD induced hepatic AHH activity at a dose of 30 micrograms/kg, while in AHH responsive C57 mouse strain, six PCDF isomers besides TCDD could enhance the enzyme activity significantly. 2,3,7,8-Tetrachlorodibenzofuran (2,3,7,8-TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1,2,3,7,8-PCDF) and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) showed the highest AHH inducing activity among the PCDF isomers tested. In contrast with the results obtained from the mouse experiments, in human lymphoblastoid cells, 2,3,4,7,8-PCDF, 1,2,3,4,6,7-hexachlorodibenzofuran (1,2,3,4,6,7-HCDF) and 1,2,3,7,8-hexachlorodibenzofuran (1,2,3,4,7,8-HCDF) elicited the highest AHH induction and were as potent AHH inducers as TCDD. These observations suggest that toxicities of 2,3,4,7,8-PCDF, 1,2,3,4,6,7-HCDF and 1,2,3,4,7,8-HCDF in human tissues may be comparable to that of TCDD. It was also observed that in both male and female human cell lines, the degree of AHH inducibilities of these compounds were roughly parallel to that of 3-methylcholanthrene, possibly indicating that genetic susceptibility among human population to the toxic compounds are also present similar to those reported among mouse strains.

Aryl hydrocarbon hydroxylase activity levels in the hepatic microsomal fraction from MC- or TCDD-treated mice: a comparison between aromatic hydrocarbon responsive and non-responsive strains

The effects of in vivo administration of polycyclic aromatic hydrocarbons on the levels of aryl hydrocarbon hydroxylase (AHH) activity in aromatic hydrocarbon (Ah) responsive and non-responsive strains of mice were studied using the hepatic microsomal fraction. Injection of 3-methylcholanthrene (MC; 42 mg/kg body wt.) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 120 micrograms/kg body wt.) into both strains produced marked enhancement of AHH activity except for MC treatment of Ah non-responsive strains. Addition of 7,8-benzoflavone (BNF) to the microsomal AHH assay mixture prepared from mice previously injected with vehicle (olive oil) alone caused an increase in activity when the mice were responsive, while BNF lowered the activity in non-responsive strains. With regard to MC-injected mice, BNF and 3-methyl-sulphonyl-4,5,3,4-tetrachlorobiphenyl (3-MSF-TCB) decreased microsomal AHH activity in Ah-responsive mice, whereas these drugs enhanced the activity in Ah-non-responsive strains. 3-MSF-TCB also had inhibitory potency on AHH activity, but the mechanism of inhibition seems to be somewhat different from that of BNF. It may also suggest that cytochrome P-450 isozymes inhibited by BNF are different from those inhibited by 3-MSF-TCB.

Effects of 3-methylsulphonyl-4,5,3′,4′-tetrachlorobiphenyl and 7,8-benzoflavone on mouse liver aryl hydrocarbon hydroxylase activity in vitro

The activity of aryl hydrocarbon hydroxylase (AHH) in mouse liver microsomes was assayed in the presence of 3-methylsulphonyl-4,5,3,4-tetrachlorobiphenyl (3-MSF-TCB). The mice had been previously injected with a fixed amount of the AHH inducer 3-methylcholanthrene (MC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or with the vehicle (olive oil) alone. The dose-effect patterns for 3-MSF-TCB were markedly different according to the genetic responsiveness of the mice towards aromatic hydrocarbons (Ah responsiveness); in Ah responsive strains 3-MSF-TCB inhibited the MC-induced AHH activity as did 7,8-benzoflavone (ANF), which is known to be a potent inhibitor of AHH, whereas in Ah non-responsive strains 3-MSF-TCB (and ANF) greatly enhanced the same activity. On the other hand, the dose-response patterns were similar for both types of mice for TCDD-induced activity or basal activity (mice injected with the vehicle alone). The dose-effect curves for 3-MSF-TCB were quite distinct from those for ANF, particularly with respect to the basal AHH activity, for both Ah responsive and non-responsive strains. These results indicate that both ANF and 3-MSF-TCB can have either an inhibitory or an activating effect on AHH, depending on the dose, the Ah phenotype and previous induction with MC or TCDD.