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Blood chemistry, alpha-fetoprotein and hepatitis B surface antigen in Yusho
Journal of Dermatological Science Supplement (2005) 1, S29—S31
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Blood chemistry, alpha-fetoprotein and hepatitis B surface antigen in Yusho Hiroshi Tsuji*, Yasuo Ito on behalf of the Study Group for Yusho Department of Internal Medicine, Kitakyushu-Tsuyazaki Hospital, Watari 1693, Tsuyazaki-machi, Fukuoka 811-3307, Japan KEYWORDS Alpha-fetoprotein; Blood chemistry; Hepatitis B surface antigen (HBsAg); Polychlorinated dibenzofurans (PCDFs); Yusho
Summary Background and Objective: An incident of accidental human exposure to polychlorinated biphenyls (PCBs) occurred in the western part of Japan in 1968. The disease is known as Yusho, because its cause was the ingestion of rice bran oil that was contaminated with PCBs. The various symptoms such as acneform skin eruptions were observed in the early stage in Yusho patients. An important fact is that polychlorinated dibenzofurans (PCDFs) were detected in the contaminated rice oil. PCDFs have a much higher toxicity than do PCBs. Analysis of blood concentration of PCDFs was performed throughout Japan in 2002. There have been no reports on the relationship between blood concentration of PCDFs and blood chemistry, alphafetoprotein or hepatitis B surface antigen (HBsAg) in Yusho. This is the first study to report on the relationship between blood concentration of PCDFs and blood chemistry, alpha-fetoprotein or HBsAg in Yusho. Methods: We analyzed blood chemistry by measuring the following 20 items–—total protein, serum albumin, alanine and aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, highdensity lipoprotein (HDL) cholesterol, triglyceride, glucose, amylase, creatine kinase, urea nitrogen, creatinine and uric acid. Alpha-fetoprotein and HBsAg were also measured. We studied the relationship between blood concentrations of total PCDFs and the items of the blood chemistry analysis, alpha-fetoprotein and HBsAg. Results: Of the 20 items of blood chemistry, alpha-fetoprotein and HBsAg, we found three items (GGT, HDL cholesterol and creatinine) were significantly related to the total PCDF level using three-way analysis of variance (ANOVA). Conclusion: A significant relationship between three items of the blood chemistry analysis (GGTP, HDL cholesterol and creatinine) and total PCDF levels in the blood was observed in 2002. The blood concentrations of total PCBs and PCDFs have now decreased; however, the PCDFs in patients with Yusho still affect blood chemistry. # 2004 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
* Corresponding author. Tel.: +81 940 52 0034; fax: +81 940 52 2779. E-mail address: [email protected] (H. Tsuji). 1574-0757/$30.00 # 2004 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. doi:10.1016/j.descs.2005.03.005
S30
1. Introduction In 1968, an incident of accidental human exposure to polychlorinated biphenyls (PCBs) occurred in the western part of Japan [1]. The disease is known today as Yusho, oil disease, because its cause was the ingestion of rice bran oil that was contaminated with PCBs used as a coolant in the manufacturing process. The various symptoms such as acneform skin eruptions and many constitutional symptoms observed in the early stage in Yusho patients have gradually improved since the incident, although blood PCB levels are still higher in these patients compared with the general population. An important fact is that polychlorinated dibenzofurans (PCDFs) were detected in the contaminated rice oil [2]. PCDFs have a much higher toxicity than do PCBs [3]. However, there have been no reports describing the effect of PCDFs on blood chemistry, alpha-fetoprotein or hepatitis B surface antigen (HBsAg). In the present study, we examined the blood chemistry, alpha-fetoprotein and HBsAg in patients with Yusho, and we studied the relation with blood concentration of PCDFs using statistical analyses.
2. Materials and methods
H. Tsuji, Y. Ito
following furans: 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, 2,3,4,6,7,8-hexachlorodibenzofuran, 1,2,3,7,8,9hexachlorodibenzofuran, 1,2,3,4,6,7,8-heptachlorodibenzofuran, 1,2,3,4,7,8,9-heptachlorodibenzofuran, and octachlorodibenzofuran. Total PCDF values and the toxic equivalent quantity (TEQ) were calculated. The data were analyzed using a three-way analysis of variance (ANOVA) model. The total PCDF value proved to be most suitable for this analysis. The dependent variable was the logarithmic value of the blood concentration of total PCDFs. Sex and age were independent variables. A P-value less than 0.10 was considered statistically significant when the item had no interaction with sex and/or age.
3. Results The relationships between blood concentrations of total PCDFs and each of the 20 items of blood Table 1 The 20 items of the blood chemistry analysis, alpha-fetoprotein and HBsAg and the statistical relevance to blood concentrations of PCDF P
2.1. Participants and investigation items In 2002, the blood concentrations of PCDFs were studied in 279 patients with Yusho. A fasting blood sample was taken for the analyses. The following 20 items of blood chemistry were measured using an autoanalyzer (Hitachi 7150, Hitachi Ltd., Tokyo, Japan): total protein, serum albumin, alanine and aspartate aminotransferase (ALT and AST), lactate dehydrogenase (LDH), alkaline phosphatase, leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, amylase, creatine kinase (CK), urea nitrogen, creatinine and uric acid. The tumor marker alpha-fetoprotein was measured by radioimmunoassay techniques (Eiken Chemical Co., Japan). The presence or absence of HBsAg was determined by standard radioimmunoassay techniques (Dinabbott, Tokyo, Japan).
2.2. Investigation and statistical methods The concentrations of PCDFs in the blood were determined with a high-resolution gas chromatograph and a high-resolution mass spectrometer equipped with a solvent-cut large volume injection system [4]. Blood samples were analyzed for the 10
Total protein Albumin ALT AST LDH Alkaline phosphatase LAP GGT Total bilirubin Conjugated bilirubin Cholinesterase Total cholesterol HDL cholesterol Triglyceride Glucose Amylase CK Urea nitrogen Creatinine Uric acid Alpha-fetoprotein HBsAg
0.129 0.887 0.349 0.129 0.382 0.308 0.262 0.068a 0.029a,b 0.150 0.401 0.944 0.077a 0.105 0.569 0.558 0.309 0.169 0.081a 0.161 0.945 0.874
ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDH: lactate dehydrogenase; LAP: leucine aminopeptidase; GGT: gamma-glutamyl transferase; HDL cholesterol: high-density lipoprotein cholesterol; CK: creatine kinase; HBsAg: hepatitis B surface antigen. a P < 0.10. b The item had interaction with sex.
Blood chemistry, alpha-fetoprotein and hepatitis B surface antigen in Yusho
chemistry, including total protein, serum albumin, ALT, AST, LDH, alkaline phosphatase, LAP, GGT, total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, HDL cholesterol, triglyceride, glucose, amylase, CK, urea nitrogen, creatinine and uric acid; and alpha-fetoprotein; and HBsAg are shown in Table 1. The following three items were significantly related to total PCDF level: GGT (P = 0.068), HDL cholesterol (P = 0.077) and creatinine (P = 0.081). The P-value of total bilirubin was 0.029; however, the item had interaction with sex.
4. Discussion It has been reported that blood PCB concentration is associated with blood chemistry, including triglyceride, total cholesterol, GGT, total bilirubin and conjugated bilirubin, in patients with Yusho [5—8]. However, there have been no reports describing the effect of PCDFs on blood chemistry, alpha-fetoprotein or HBsAg. In this study, the relationship between the blood PCDF concentration and blood chemistry, alpha-fetoprotein or HBsAg was investigated for the first time using three-way ANOVA. Of the 20 items of the blood chemistry analysis, total PCDF value was significantly related to three items (GGT, HDL cholesterol and creatinine). This is the first report of a statistical analysis of the relationship between PCDFs and blood chemistry, alphafetoprotein and HBsAg in Yusho patients. Further study is necessary to assess the exact relationship between the effects of PCDFs on blood chemistry, alpha-fetoprotein and HBsAg.
S31
Acknowledgement This work was supported in part by a Grant-in-Aid for scientific research from the Ministry of Health, Labour and Welfare, Japan.
References [1] Kuratsune M, Yoshimura T, Matsuzaka J, Yamaguchi A. Epidemiologic study on Yusho, a poisoning caused by ingestion of rice oil contaminated with a commercial brand of polychlorinated biphenyls. Environ Health Perspect 1972;1:119— 28. [2] Hayabuchi H, Yoshimura T, Kuratsune M. Consumption of toxic rice oil by ‘Yusho’ patients and its relation to the clinical response and latent period. Food Cosmet Toxicol 1979;17: 455—61. [3] Oishi S, Morita M, Fukuda H. Comparative toxicity of polychlorinated biphenyls and dibenzofurans in rats. Toxicol Appl Pharmacol 1978;43:13—22. [4] Todaka T, Hirakawa H, Tobiishi K, Iida T. New protocol of dioxins analysis in human blood. Fukuoka Igaku Zasshi 2003; 94:148—57. [5] Tsuji H, Akagi K, Murai K, Kajiwara E, Fujishima M. Liver damage and hepatocellular carcinoma in patients with Yusho. Fukuoka Igaku Zasshi 1987;78:343—8. [6] Murai K, Tsuji H, Fujishima M. Renal function in patients with Yusho. Fukuoka Igaku Zasshi 1989;80:318—23. [7] Hirota Y, Hirohata T, Kataoka K, Shinohara S, Tokiwa H. Laboratory findings in the medical examination of chronic ‘‘Yusho’’ (PCB Poisoning) patients: with special reference to blood PCB and serum triglyceride. Fukuoka Igaku Zasshi 1993; 84:287—93. [8] Tsuji H, Ikeda K, Suzuki N, Fujishima M. Laboratory findings in patients with Yusho: 26 year follow-up study. Fukuoka Igaku Zasshi 1995;86:273—6.
www.intl.elsevierhealth.com/journals/jods
Blood chemistry, alpha-fetoprotein and hepatitis B surface antigen in Yusho Hiroshi Tsuji*, Yasuo Ito on behalf of the Study Group for Yusho Department of Internal Medicine, Kitakyushu-Tsuyazaki Hospital, Watari 1693, Tsuyazaki-machi, Fukuoka 811-3307, Japan KEYWORDS Alpha-fetoprotein; Blood chemistry; Hepatitis B surface antigen (HBsAg); Polychlorinated dibenzofurans (PCDFs); Yusho
Summary Background and Objective: An incident of accidental human exposure to polychlorinated biphenyls (PCBs) occurred in the western part of Japan in 1968. The disease is known as Yusho, because its cause was the ingestion of rice bran oil that was contaminated with PCBs. The various symptoms such as acneform skin eruptions were observed in the early stage in Yusho patients. An important fact is that polychlorinated dibenzofurans (PCDFs) were detected in the contaminated rice oil. PCDFs have a much higher toxicity than do PCBs. Analysis of blood concentration of PCDFs was performed throughout Japan in 2002. There have been no reports on the relationship between blood concentration of PCDFs and blood chemistry, alphafetoprotein or hepatitis B surface antigen (HBsAg) in Yusho. This is the first study to report on the relationship between blood concentration of PCDFs and blood chemistry, alpha-fetoprotein or HBsAg in Yusho. Methods: We analyzed blood chemistry by measuring the following 20 items–—total protein, serum albumin, alanine and aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, highdensity lipoprotein (HDL) cholesterol, triglyceride, glucose, amylase, creatine kinase, urea nitrogen, creatinine and uric acid. Alpha-fetoprotein and HBsAg were also measured. We studied the relationship between blood concentrations of total PCDFs and the items of the blood chemistry analysis, alpha-fetoprotein and HBsAg. Results: Of the 20 items of blood chemistry, alpha-fetoprotein and HBsAg, we found three items (GGT, HDL cholesterol and creatinine) were significantly related to the total PCDF level using three-way analysis of variance (ANOVA). Conclusion: A significant relationship between three items of the blood chemistry analysis (GGTP, HDL cholesterol and creatinine) and total PCDF levels in the blood was observed in 2002. The blood concentrations of total PCBs and PCDFs have now decreased; however, the PCDFs in patients with Yusho still affect blood chemistry. # 2004 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
* Corresponding author. Tel.: +81 940 52 0034; fax: +81 940 52 2779. E-mail address: [email protected] (H. Tsuji). 1574-0757/$30.00 # 2004 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. doi:10.1016/j.descs.2005.03.005
S30
1. Introduction In 1968, an incident of accidental human exposure to polychlorinated biphenyls (PCBs) occurred in the western part of Japan [1]. The disease is known today as Yusho, oil disease, because its cause was the ingestion of rice bran oil that was contaminated with PCBs used as a coolant in the manufacturing process. The various symptoms such as acneform skin eruptions and many constitutional symptoms observed in the early stage in Yusho patients have gradually improved since the incident, although blood PCB levels are still higher in these patients compared with the general population. An important fact is that polychlorinated dibenzofurans (PCDFs) were detected in the contaminated rice oil [2]. PCDFs have a much higher toxicity than do PCBs [3]. However, there have been no reports describing the effect of PCDFs on blood chemistry, alpha-fetoprotein or hepatitis B surface antigen (HBsAg). In the present study, we examined the blood chemistry, alpha-fetoprotein and HBsAg in patients with Yusho, and we studied the relation with blood concentration of PCDFs using statistical analyses.
2. Materials and methods
H. Tsuji, Y. Ito
following furans: 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, 2,3,4,6,7,8-hexachlorodibenzofuran, 1,2,3,7,8,9hexachlorodibenzofuran, 1,2,3,4,6,7,8-heptachlorodibenzofuran, 1,2,3,4,7,8,9-heptachlorodibenzofuran, and octachlorodibenzofuran. Total PCDF values and the toxic equivalent quantity (TEQ) were calculated. The data were analyzed using a three-way analysis of variance (ANOVA) model. The total PCDF value proved to be most suitable for this analysis. The dependent variable was the logarithmic value of the blood concentration of total PCDFs. Sex and age were independent variables. A P-value less than 0.10 was considered statistically significant when the item had no interaction with sex and/or age.
3. Results The relationships between blood concentrations of total PCDFs and each of the 20 items of blood Table 1 The 20 items of the blood chemistry analysis, alpha-fetoprotein and HBsAg and the statistical relevance to blood concentrations of PCDF P
2.1. Participants and investigation items In 2002, the blood concentrations of PCDFs were studied in 279 patients with Yusho. A fasting blood sample was taken for the analyses. The following 20 items of blood chemistry were measured using an autoanalyzer (Hitachi 7150, Hitachi Ltd., Tokyo, Japan): total protein, serum albumin, alanine and aspartate aminotransferase (ALT and AST), lactate dehydrogenase (LDH), alkaline phosphatase, leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, amylase, creatine kinase (CK), urea nitrogen, creatinine and uric acid. The tumor marker alpha-fetoprotein was measured by radioimmunoassay techniques (Eiken Chemical Co., Japan). The presence or absence of HBsAg was determined by standard radioimmunoassay techniques (Dinabbott, Tokyo, Japan).
2.2. Investigation and statistical methods The concentrations of PCDFs in the blood were determined with a high-resolution gas chromatograph and a high-resolution mass spectrometer equipped with a solvent-cut large volume injection system [4]. Blood samples were analyzed for the 10
Total protein Albumin ALT AST LDH Alkaline phosphatase LAP GGT Total bilirubin Conjugated bilirubin Cholinesterase Total cholesterol HDL cholesterol Triglyceride Glucose Amylase CK Urea nitrogen Creatinine Uric acid Alpha-fetoprotein HBsAg
0.129 0.887 0.349 0.129 0.382 0.308 0.262 0.068a 0.029a,b 0.150 0.401 0.944 0.077a 0.105 0.569 0.558 0.309 0.169 0.081a 0.161 0.945 0.874
ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDH: lactate dehydrogenase; LAP: leucine aminopeptidase; GGT: gamma-glutamyl transferase; HDL cholesterol: high-density lipoprotein cholesterol; CK: creatine kinase; HBsAg: hepatitis B surface antigen. a P < 0.10. b The item had interaction with sex.
Blood chemistry, alpha-fetoprotein and hepatitis B surface antigen in Yusho
chemistry, including total protein, serum albumin, ALT, AST, LDH, alkaline phosphatase, LAP, GGT, total bilirubin, conjugated bilirubin, cholinesterase, total cholesterol, HDL cholesterol, triglyceride, glucose, amylase, CK, urea nitrogen, creatinine and uric acid; and alpha-fetoprotein; and HBsAg are shown in Table 1. The following three items were significantly related to total PCDF level: GGT (P = 0.068), HDL cholesterol (P = 0.077) and creatinine (P = 0.081). The P-value of total bilirubin was 0.029; however, the item had interaction with sex.
4. Discussion It has been reported that blood PCB concentration is associated with blood chemistry, including triglyceride, total cholesterol, GGT, total bilirubin and conjugated bilirubin, in patients with Yusho [5—8]. However, there have been no reports describing the effect of PCDFs on blood chemistry, alpha-fetoprotein or HBsAg. In this study, the relationship between the blood PCDF concentration and blood chemistry, alpha-fetoprotein or HBsAg was investigated for the first time using three-way ANOVA. Of the 20 items of the blood chemistry analysis, total PCDF value was significantly related to three items (GGT, HDL cholesterol and creatinine). This is the first report of a statistical analysis of the relationship between PCDFs and blood chemistry, alphafetoprotein and HBsAg in Yusho patients. Further study is necessary to assess the exact relationship between the effects of PCDFs on blood chemistry, alpha-fetoprotein and HBsAg.
S31
Acknowledgement This work was supported in part by a Grant-in-Aid for scientific research from the Ministry of Health, Labour and Welfare, Japan.
References [1] Kuratsune M, Yoshimura T, Matsuzaka J, Yamaguchi A. Epidemiologic study on Yusho, a poisoning caused by ingestion of rice oil contaminated with a commercial brand of polychlorinated biphenyls. Environ Health Perspect 1972;1:119— 28. [2] Hayabuchi H, Yoshimura T, Kuratsune M. Consumption of toxic rice oil by ‘Yusho’ patients and its relation to the clinical response and latent period. Food Cosmet Toxicol 1979;17: 455—61. [3] Oishi S, Morita M, Fukuda H. Comparative toxicity of polychlorinated biphenyls and dibenzofurans in rats. Toxicol Appl Pharmacol 1978;43:13—22. [4] Todaka T, Hirakawa H, Tobiishi K, Iida T. New protocol of dioxins analysis in human blood. Fukuoka Igaku Zasshi 2003; 94:148—57. [5] Tsuji H, Akagi K, Murai K, Kajiwara E, Fujishima M. Liver damage and hepatocellular carcinoma in patients with Yusho. Fukuoka Igaku Zasshi 1987;78:343—8. [6] Murai K, Tsuji H, Fujishima M. Renal function in patients with Yusho. Fukuoka Igaku Zasshi 1989;80:318—23. [7] Hirota Y, Hirohata T, Kataoka K, Shinohara S, Tokiwa H. Laboratory findings in the medical examination of chronic ‘‘Yusho’’ (PCB Poisoning) patients: with special reference to blood PCB and serum triglyceride. Fukuoka Igaku Zasshi 1993; 84:287—93. [8] Tsuji H, Ikeda K, Suzuki N, Fujishima M. Laboratory findings in patients with Yusho: 26 year follow-up study. Fukuoka Igaku Zasshi 1995;86:273—6.