Hiroto Nakadaira

Effects of low-dose cadmium exposure on biological examinations.

We conducted an epidemiological study to investigate the effects of low-dose cadmium (Cd) exposure on human health in a specific area of a town in Japan where low Cd concentration was detected in rice. We compared clinical findings, urinary and whole blood Cd concentrations, and indicators of renal dysfunction between the polluted area and the control area. The study employed 44 men and 54 women from the polluted area and 21 men and 29 women from the control area. In urine analysis, as indicators of Cd exposure and possible related renal dysfunction, Cd, beta(2)-microglobulin (beta(2)-MG), alpha(1)-microglobulin (alpha(1)-MG), N-acetyl-beta-D-glucosaminidase (NAG), total protein, inorganic phosphorus, lysozyme and creatinine were quantitatively measured. In blood analysis, serum IP and creatinine and whole blood Cd were measured. No case of renal dysfunction due to Cd exposure was confirmed. However, both the urinary and whole blood Cd of the polluted area were significantly higher than those of the control area for both sexes. Urinary beta(2)-MG did not differ between the two areas. For women, urinary alpha(1)-MG was significantly higher in the polluted area than in the control area. In correlation analysis, beta(2)-MG, alpha(1)-MG and NAG, were positively correlated with both of urinary and whole blood Cd for men and women in the polluted area except for between urinary beta(2)-MG and urinary Cd for men. In the control area, the sole positive correlation observed was between urinary beta(2)-MG and whole blood Cd for men. We then examined the determinants of variations of parameters in urinary and blood tests. Potential determinants were age, sex, body mass index, an indicator of smoking habits (cigarette index) and the index of estimated Cd intake from rice (Cd-rice-index). Cd-rice-index was expressed as the product of Cd concentrations in homegrown rice multiplied by daily frequency multiplied by duration (years) of residence in the polluted area. In multiple regression analysis, whole blood Cd was independently associated with Cd-rice-index, age and gender. Variations in whole blood Cd accounted for a substantial portion of the variations in urinary Cd, although they were less influential in older individuals. Whole blood Cd was the sole independent variable related to variations in urinary beta(2)-MG. Cd-rice-index accounted for a portion of the variance in urinary NAG, while age was a more powerful determinant. It was thus revealed that the consumption of homegrown rice polluted with Cd in low concentration resulted in an elevation of whole blood Cd level and consequent increase in urinary Cd level. However, it was not clearly elucidated that the excretion of urinary low-molecular microglobulins could increase significantly in response to slight elevation of Cd body load.

Elevated mortality from lung cancer associated with arsenic exposure for a limited duration.

In 1959, arsenic poisoning was detected in the town of Nakajo in Japan. The cause was exposure to inorganic arsenic in well water during 1954 to 1959. To examine the long-term effects of limited-duration arsenic exposure, we conducted mortality and survival studies for patients with chronic arsenic exposure and for control subjects from 1959 to 1992. The ratio of observed deaths to expected deaths from lung cancer was significantly high (7:0.64) for male patients. The lung cancer mortality rate was elevated markedly in subgroups with higher clinical severities of symptoms. Small cell carcinoma was specific to the exposed patients. The cumulative chance of survival declined significantly in the exposed patients compared with the controls. The decline disappeared when lung cancer deaths were treated as lost to follow-up. The results showed that a 5-year period of arsenic exposure was associated with risk of lung cancer.

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Geographic Clustering Patterns in Mortality from Biliary Tract Cancer in Japan

We calculated the standardized mortality ratios (SMRs) of biliary tract cancer (BTC) in Japan from 1981 to 1990 and statistically analyzed the results according to 333 Secondary Areas of Medical Care, as well as sex and subsite [gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC)], in order to examine geographic clustering patterns of BTC. In GBC in both sexes, the Secondary Areas of Medical Care with high SMRs were clustered in the eastern part of Japan. In BDC in both sexes, the Areas with high SMRs were clustered between the northern and eastern parts of Japan. In comparison with GBC, this clustering favored the northern part of Japan. In males, the clustering pattern in mortality from BTC was mainly due to the occurrence of BDC. In females, the clustering pattern in mortality from BTC reflected that of GBC. The clustering of BTC, especially GBC, seems to be related to the distribution of plains, basins, and rivers.

Determination of Free Fatty Acids in Human Bile by High-Performance Liquid Chromatography

We developed a high-performance liquid chromatography (HPLC) method for free fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from bile in a single step using an Isolute™ ODS cartridge, derivatized with 9-anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with carboxylic acid at room temperature. Then, HPLC was used for separating and quantifying FFAs. This method proved to be simple and time-saving. The mean recovery of FFA added to human gallbladder bile was 97.6%, and the detection limit was 100–250 pg. Using this method, we determined FFA concentrations in the gallbladder bile of 11 gallstone patients. The mean concentration of total FFA was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

Distribution of selenium and molybdenum and cancer mortality in Niigata, Japan

Selenium and molybdenum have inhibitory effects on gastrointestinal carcinogenesis. We investigated the levels of selenium and molybdenum in sediments and mortality from cancers at specific sites in 19 areas of Niigata Prefecture, Japan, and compared these factors. The average concentrations of selenium and molybdenum were 0.44 +/- 0.19 ppm (micrograms/g dry weight; mean +/- standard deviation) and 3.82 +/- 1.03 ppm, respectively. Selenium was not associated significantly with cancer mortality. There were inverse correlations between molybdenum levels and female mortality from cancers of the esophagus (r = -.446, .05 < p < .1) and rectum (r = -.529, p < .05). Molybdenum was correlated positively with female mortality from cancer of the pancreas (r = .603, p < .01). Further investigations are needed for causal interpretation of these results.

Co-mutagenicity of glyco- and tauro-deoxycholic acids in the Ames test.

Mutagenicity and co-mutagenicity of glyco- and tauro-deoxycholic acids (GDCA and TDCA), which are abundant in human bile, were examined by the Ames test. The two chemicals were not mutagenic for themselves to Salmonella typhimurium TA98 and TA100, with and without S9 mix. They enhanced, however, the mutagenic activities of the pro-mutagens, 2-aminoanthracene (2AA) and benzo[a]pyrene (BaP), for both TA98 and TA100 with S9 mix. They were more co-mutagenic for the pro-mutagens on TA98 than on TA100. On TA98, the mutagenic activities of 2AA with GDCA (5 mumol/plate) and with TDCA (5 mumol/plate) were 9.7-fold and 11.8-fold as high as that of the corresponding control (2AA only), respectively. BaP with GDCA (2.5 mumol/plate) and with TDCA (2.5 mumol/plate) showed 2.8-fold and 3.0-fold increases over the corresponding control level (BaP only), respectively. It is hence concluded that GDCA and TDCA may enhance the activity of some mutagens existing in bile.

Mental and Physical Effects of Tanshin funin, Posting without Family, on Married Male Workers in Japan

Mental and Physical Effects of Tanshin funin, Posting without Family, on Married Male Workers in Japan: Hiroto Nakadaira, et al. Division of Social and Environmental Medicine, Department of Community Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences—This paper investigates the effects of tanshin funin, a posting without family, on the health of married male workers. A prospective study using the pair‐matched method was performed. One hundred and twenty‐nine married male tanshin funin workers in their 40s and 50s and as many matched workers living with their family (regular workers) participated. Fewer tanshin funin workers took breakfast everyday (OR=3.3, p<0.001). Tanshin funin workers more frequently suffered from stress due to daily chores (OR=3.6, p<0.001) and from stress‐related health problems, namely headache (OR=4.7, p=0.013) and gastric/ duodenal ulcers (OR=8.7, p<0.001). They also developed more frequently common cold/bronchitis (OR=14.5, p<0.001). The levels of γ‐glutamyl transpeptidase for workers reluctant to work under tanshin funin and workers who spent less than two years in tanshin funin increased significantly from the fiscal year 1997 to year 2001 (46.7 to 67.5 IU/l, p<0.001, and 36.9 to 72.4 IU/l, p=0.005, respectively), although those of their matched regular workers did not show significant changes. The daily alcohol intake of reluctant tanshin funin workers (the equivalent of approximately 817 ml of beer) was higher than that of the matched regular workers (582 ml, p=0.026). In summary, abrupt changes in lifestyle and elevated mental stress were thus important effects of tanshin funin. Tanshin funin workers should be provided with health and lifestyle education programs and mental health care before and during tanshin funin. Doctors and nurses in the healthcare departments of companies should play a leading role.

Effects of selenium on gallbladder carcinogenesis induced by an intracholecystic 3-methylcholanthrene beeswax pellet in female Syrian golden hamsters

This study represents the first report of the effects of selenium (Se) on chemically induced gallbladder carcinogenesis in hamsters. A total of 100 female Syrian golden hamsters was randomly assigned to four groups, which groups of 25 hamsters were given ad libitum drinking water containing either 0.0, 0.5, 2.0 or 4.0 ppm Se (as sodium selenite) for 24 weeks. Initiation was performed at week 4 by the insertion of a Beeswax pellet containing 3-methylcholanthrene (3-MC) into the gallbladder. The incidence of total malignant tumors at the end of the study (24 weeks) was 88, 75, 81 and 82% in the 0.0, 0.5, 2.0 and 4.0 ppm Se groups, respectively. All the cases of carcinoma but two were considered to develop through the sequence from dysplasia to carcinoma in situ (CIS) and from CIS to adenocarcinoma of invasive type. The incidence of CIS was significantly lower in hamsters treated without Se than in those treated with Se (P < 0.05). On the other hand, the incidence of invasive adenocarcinoma was significantly higher in the former than in the latter (P < 0.05). These results were summarized that Se might retard the progression of hamster gallbladder carcinogenesis induced by a 3-MC beeswax pellet.

Concentration of Metals and Other Elements in the Hair of Easter Islanders

HIROTO NAKADAIRA Division of Social and Environmental Medicine Department of Community Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences Niigata, Japan IVAN SERRA School of Public Health University of Chile Santiago, Chile MASAHARU YAMAMOTO Division of Social and Environmental Medicine Department of Community Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences Niigata, Japan RUTH ROGERS DAVID GUTIERREZ Hospital Hanga Roa lsla de Pascua (Easter Island) San Antonio, Chile