Masanori Kuratsune

A Case‐Control Study of Gastric Cancer and Diet in Northern Kyushu, Japan

A case‐control study of gastric cancer was done in a rural area of northern Kyushu, Japan, in relation to dietary habits especially focusing on the relationship with the consumption of broiled fish. The study was based upon 139 cases of newly diagnosed gastric cancer at a single institution, 2,574‐ hospital controls and 278 controls sampled randomly from the residents of the study area (with sex and year of birth matched). No association was observed between the consumption of broiled fish and gastric cancer risk whether three types of broiled fish (raw fish, dried fish and salted fish) were analyzed separately or as a single category. However, consistently in the comparisons with both sets of controls, the risk of gastric cancer was inversely related with the consumption of fruits and positively associated with cigarette smoking. A decreased risk of gastric cancer was also noted among those with high consumption of green tea (10 or more cups per day).

Determination of polychlorinated dibenzofurans in tissues of patients with 'yusho'.

Abstract Tissues of patients with ‘Yusho’ and of persons not suffering from this disease were analysed for polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) by column chromatography, gas chromatography, and gas chromatography-mass spectrometry. Both PCBs and PCDFs were identified in the tissues of patients with Yusho, while only PCBs were detected in the tissues of the other persons studied. In contrast to the PCBs, which were found far more in the adipose tissue than in the liver, PCDFs occurred in very similar concentrations in these two types of tissue. The persisting PCDFs in the tissues of Yusho patients were almost exclusively penta and hexachloro derivatives.

Comparison of causal agents in Taiwan and Fukuoka PCB poisonings

INTRODUCTION In 1968, more than 1,500 persons in western Japan were in tox ica ted by consuming a commercial r ice oil contaminated w i th Kanechlor 400 (KC-q00) , a Japanese b rand of po lych lor ina ted b ipheny ls (PCBs) (1 -2 ) . The causal oil was found to contain not only PCBs but also ve ry tox ic po lych lo r i hated d ibenzofurans (PCDFs) (3) and po lych lor ina ted qua te rpheny ls (PCQs) wi th yet unc lar i f ied tox i c i t y (4 -6 ) . In 1979, eleven years a f te r the Japanese inc ident (Yusho ) , a s imi lar mass food poisoning recu r red in the Centra l Taiwan and the pat ients to ta l led neary 2,000. The cooking oil consumed by the pat ients was also contaminated wi th PCBs, PCDFs, and PCQs (7 -9 ) . To fu l l y unders tand the e t io logy of both po ison ings, i t is necessary to inves t iga te i f the two tox ic r ice oi ls used in Japan and Taiwan contain d i f f e ren t components of PCBs and PCDFs, as PCBs and PCDFs consist of many congeners . Above al l , examinat ion of PCDF components is ve ry impor tan t , because some PCDF congeners are much more tox ic than those of PCBs (10) . We analyzed samples of r ice oil which caused the poisoning in Taiwan and the blood from the pat ients for PCB and PCDF congeners and compared these resu l ts w i th those of Japanese cases (3, 11-12). We also est imated the concent ra t ions of PCQs in both the r ice oi ls .

Yusho, a poisoning caused by rice oil contaminated with polychlorinated biphenyls.

SPORADIC outbreaks of a peculiar skin disease were reported in Fukuoka-Ken (Fukuoka Prefeeture), Japan, in early October 1968. It was charaeterized by sueh symptoms as follicular accentuation, acneform eruption, pigmentation of the skin and nails, and hypersecretion of the Meibomian gland. Staff members of the department of dermatology of the Faculty of Medicine, Kyushu University, Fukuoka, who examined some of the early patients suspected they had chloraene. A possible causal relationship between the disease and ingestion of a certain brand of rice oil was also suspected in view of the distinet familial aggregation of the patients and their common use of the oil (1). This relationship was subsequently proved, and the disease was called Yusho, or rice oil disease. To elarify the cause of the epidemic, a study group headed by Prof. S. Katsuki of the Kyushu University Faculty of Medicine was organized by the staff of that university, the School of Medicine of Kurume University, and local health departments. An epidemiologic study subgroup was set up within the study group on October 19, 1968, which was directed by Kuratsune and also included the other three authors. This subgroup immnediately designed and carried out a series of extensive surveys in close cooperation with the department of hygiene of our faculty of medicine and the departments of public health of the Prefecture of Fukuoka and of the cities of Kitakyushu, Fukuoka, and Ohmuta. The epidemic spread not only over FukuokaKen but also over 20 other prefectures in the western part of Japan. It produced 1,001 patients -502 males and 499 females-according to the latest tabulation by the section of food hygiene, Ministry of Welfare. Although our study of the epidemic was confined to Fukuoka-Ken, and the epidemic proved to be caused by accidentally contaminated oil, we believe that publication of our results will help prevent similar food poisonings. These incidents can occur anywhere in the world if sufficient care is not exercised.

Consumption of toxic rice oil by ‘yusho’ patients and its relation to the clinical response and latent period

Abstract The amounts of toxic rice oil consumed individually by 141 patients with Yusho were estimated, taking into consideration their age and sex and the frequency of meals eaten at home. Since the total amount of oil consumed, the amount of oil consumed per kg per day, the amount of oil consumed during the latent period and the length of the latent period each showed a positively skew distribution, geometric means were calculated for all of them. The amounts of polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs) and polychlorinated quaterphenyls (PCQs) taken by the patients were, on average, 633, 3·4 and 596 mg, respectively, in total or 157, 0·9 and 148 hg/kg/day. The mean latent period was estimated to be 71 days, and the amounts of PCBs, PCDFs, and PCQs taken during the latent period were calculated to be, on average, 466, 2·5 and 439 mg, respectively, the smallest amounts taken by a patient during the latent period being estimated to be 111, 0·6 and 105 mg, and the smallest doses 29, 0·16 and 27 μg/kg/day, respectively. The clinical severity of the response showed a close positive correlation with the total amount of oil consumed but not with the amount of oil consumed per kg per day. The latent period and the amount of oil consumed per kg per day showed a highly significant negative correlation.

Transfer of polychlorinated biphenyls to the foetuses and offspring of mice.

Abstract Mice were fed Kanechlor-500 (KC-500) at a dietary level of 0·01 (control). 0·94, 8·4 or 86 ppm from the day of insemination until day 18 of pregnancy and were then killed. The amounts of polychlorinated biphenyls (PCBs) present in the whole body, liver and foetuses of the mice were, respectively, 6-16, 0·8-3 and 0·1-0·2% of the total PCB intake, regardless of the dietary level of PCB, showing that transplacental transfer of PCBs to foetuses occurs to a relatively small degree. Other pregnant mice were fed a diet containing 0·01 or 0·94 ppm KC-500 and maintained on this until their offspring were 5 wk old. The young (one or two from each litter) were killed at weekly intervals from birth and analysed for PCBs. These offspring contained 100 or more times as much PCB during lactation as was present in the foetuses, indicating a considerable transfer of PCBs via the milk.

A comparative study of polychlorinated dibenzofurans, polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin on aryl hydrocarbon hydroxylase inducing potency in rats

The aryl hydrocarbon hydroxylase (AHH) inducing potency of toxic chlorinated aromatic hydrocarbons such as polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in the young male Wistar rats. Alternatively, a technical PCDF mixture, 15 individual PCDF isomers or TCDD were administered i.p. in doses of 5 μg/kg; a PCB mixture was given in a dose of 50 mg/kg. The order of AHH inducing ability was TCDD > PCDFs ≫ PCBs in kidney, lung, and liver. In the prostate, thymus, and spleen, only TCDD enhanced the AHH activity. The AHH inducibility in the lung and liver, induced by 15 pure PCDF isomers with varying chlorine substitutions was also examined. Only 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-tetra-CDF) and 2,3,4,7,8-pentachlorodibenzofurans (2,3,4,7,8-penta-CDF) significantly induced the hepatic AHH activity (4- and 2-fold, respectively), while eight PCDF isomers, including these two, significantly enhanced the pulmonary AHH activity (6- to 30-fold). Taking into account both the potent AHH inducibility and the high bioaccumulation of these compounds, 2,3,7,8-tetra- and 2,3,4,7,8-penta-CDF should be given due attention with regard to environmental-related factors and the possibility of involvement in the etiology of “Yusho” disease.

Transfer of polychlorinated dibenzofurans to the foetuses and offspring of mice.

Abstract A diet containing 0·6 ppm of a mixture of polychlorinated dibenzofurans (PCDFs) having 4, 5 or 6 chlorine atoms was fed to mice for 18 days after mating or for 14 days after delivery. Dams, foetuses and offspring were analysed for PCDFs by gas chromatography. PCDFs were transferred to the foetuses across the placenta and to the offspring through milk. The amounts of PCDFs transferred through milk were much larger than the amounts transferred across the placenta. A greater level of PCDFs was accumulated in the livers of the dams than in other tissues. There were differences between the PCDFs in their levels of accumulation in the tissues of the mice.

Smoking and mortalities from cancer, coronary heart disease and stroke in male Japanese physicians

SummaryA cohort of 5,477 male Japanese physicians was studied to examine the relationship between smoking habits and mortalities from cancer, coronary heart disease (CHD) and stroke over 12.7 years. The logistic regression analysis based on proportional hazard models was used for statistical assessment. The risks of both lung cancer and CHD were strongly associated with smoking habits in terms of the number of cigarettes smoked per day, inhalation level and age at starting to smoke. These associations were not influenced by the effect of drinking habits. However, the risk increment of lung cancer due to cigarette smoking was fairly small as compared with the data from other studies of male Caucasians. A statistically significant association was observed between upper aerodigestive cancer and cigarette smoking. But this relationship became insignificant after adjustment for drinking habits, and the risk of heavy smokers was drastically reduced. No clear association was noted between smoking and mortalites from gastric cancer and stroke.

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in human lymphoblastoid cells by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin

Aryl hydrocarbon hydroxylase(AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3′,4′,5′-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in human lymphoblastoid cell lines with different AHH inducibility for 3-methylcholanthrene (3-MC) obtained from healthy subjects. Each of the cell lines was treated with eitht individual PCDF isomers, TCDD, and HCB at doses of 1.9–15 ng/ml of culture medium, 1.9–7.5 ng/ml and 95 ng/ml, respectively. Lymphoblastoid cell lines were arbitrarily classified into three groups based on their AHH inducibilities with 3-MC (2.5 μM); low (3-MC/ control=I<3), middle (3<=I<6) and high (I>=6). Degrees of the enzyme inducibilities of the organochlorine compounds proportionally increased with those for 3-MC. AHH inducibilities with 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), 1,2,3,4,6,7-hexachlorodibenzofuran(1,2,3.4,6,7-HCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran(1,2,3,4,7,8-HCDF) were comparable to those of TCDD at doses of 7.5 ng/ ml, and about twice as high as those of 2,3,7,8-tetrachlorodibenzofuran (TCDF), at the same dose, HCB, at a dose of 95 ng/ ml, did not induce enzyme activity. The experimental evidence indicated that AHH inducibility by the organochlorine compounds reflected the genetic susceptibility of the cells to the phenomenon of induction, and PCDF isomers found at relatively high concentrations in tissues of mammals exerted the highest values of AHH induction.