Acute oral toxicity (LD50-value) of organic chemicals to mice was analyzed by using solubility parameter (δc), a thermodynamic parameter, of the chemicals. As it was observed in the previous study with rats, parabolic correlations were established between logarithm of LD50-value (mmol/kg body weight, mice) and δc of all the collected chemicals (n=85, R=0.626), alcohols (n=10, R=0.683), ketones (n=7, R=0.631) and aromatics (n=62, R=0.645). Introducing molar volume (Vc) to the above equations did not improve the correlations. Although statistically significant correlations were not found in alcohols and ketones with mice, we successfully assured the theoretical equation regardless of species difference by establishing significant correlations with all the collected chemicals and aromatics. By analysis, we could determine the solubility parameter of 2.27×104 (J/m3)1/2 for the biological membrane (absorption site) of mice. As the δc-values which dip the LD50-values are approximately the same for mice and rats, common deleterious effects and mechanism may be working at common target sites. In addition, no species difference in sensitivity (toxicity) was found for the aromatics. For comparison, log P was used to describe LD50 of all the collected chemicals, but no correlation was established (R=0.004-0.418).
Acute dermal toxicity (LD50-value) of organic chemicals to rabbits was analyzed by using solubility parameter (δc), a thermodynamic parameter, of the chemicals. As it was observed in the previous studies with rats and mice, parabolic correlations were also established between logarithm of LD50-value (mmol/kg body weight, rabbits) and δc of all the collected chemicals (n=56, R=0.498), alcohols (n=19, R=0.857), ketones (n=7, R=0.711), aldehydes (n=7, R=0.633) and aromatics (n=20, R=0.613). Introduction of molar volume (Vc) to the above equations did not improve the correlations. In the study, we assumed that chemicals absorbed dermally by the mammals similarly disturb the homeostasis, as in acute oral toxicities of organic chemicals to rats and mice. We successfully confirmed the theoretical equation regardless of species and routes of administration by establishing statistically significant correlations with all the collected chemicals, alcohols and aromatics. By analysis, we could determine the solubility parameter of 2.24×104 (J/m3)1/2 for the biological membrane (absorption site) of rabbits. As the dermal δc-values which dip the LD50-values for rabbits are approximately the same as in acute oral toxicities with rats and mice, common deleterious effects and mechanism may be working at the common target sites. The regression curves of LD50-values of rabbits, however, are slightly higher than those of rats and mice, which may reflect the difference in amounts of the chemicals absorbed by the body. For comparison, log P was used to describe LD50 of all the collected chemicals, and significant correlations were observed in parabolic and bilinear equation (n=56, R=0.522, 0.584), but no relationships were established for aromatics.
A homozygous gene deletion at the glutathione-S-transferase (GST) M1 locus of genomic DNA isolated from the peripheral blood was investigated for its relationship with lung and oral cancer using the polymerase chain reaction (RCR) technique. DNA samples were prepared from 91 healthy controls, 53 lung cancer patients and 48 oral cancer patients. As for the genotype, 38 of 91 healthy controls (41.7%), 27 of 53 lung cancer patients (50.9% [p>0.05], odds ratio 1.45, 95% confidence interval 0.73-2.86) and 26 of 48 oral cancer patients (54.2% [p>0.05], odds ratio 1.65, 95% confidence interval 0.82-3.32) were GSTM1 deletion types. When male-smoker patients and healthy controls were analyzed, the frequency of GSTM1 deletion genotype was 41.6% in the healthy controls and 52.2% (p>0.05, odds ratio 1.53, 95% confidence interval 0.58-4.14), 54.5% (p>0.05, odds ratio 1.68, 95% confidence interval 0.45-6.26), and 50.0% (p>0.05, odds ratio 1.40, 95% confidence interval 0.55-3.60) in pulmonary squamous cell carcinoma, small cell carcinoma, intraoral squamous cell carcinoma patients, respectively. Thus, the GSTM1 deletion genotype as a host factor predisposing to lung and oral cancer could not be confirmed in this study.
Exercise stress test is useful for the early detection of coronary artery disease and is recommended as a medical clearance test before the initiation of exercise training. However, when applied to apparently healthy people, there are many false positive results. It is therefore necessary to determine indications for stress testing, but few data are available in Japan. In this study, we performed exercise stress test in apparently healthy men to investigate the incidence of exercise-induced ST segment changes and their relationship to coronary risk factors. The subjects were 2, 187 men who underwent symptom-limited exercise stress test at a health-promotion center in Tokyo. Those with a history of cardiovascular disease were excluded. They underwent symptom-limited exercise stress test on a treadmill with a modified Bruce protocol or on a cycle ergometer with a ramp protocol (20 watts per minute). Twelve-lead electrocardiogram was recorded every 3 min. Cardiologists evaluated the exercise ECG responses, and advised those with abnormal ST segment changes (Group A) to undergo further examinations at a cardiovascular hospital. The results of further examination such as exercise scintigraphy and/or coronary angiography were obtained. Twice the number of subjects with normal exercise responses were selected as age-matched controls (Group N) to compare the coronary risk factors between the two groups. Twenty-nine subjects had abnormal ST segment changes (1.33% of the total subjects) (Group A). Their mean age was 57 years (38 to 76). Among these, 27 had ST segment depression and 2 had ST elevation. Among 1, 447 subjects under 50 years of age, 5 had abnormal ST segment changes (0.3%), and among 740 subjects over 50 years of age, 24 had abnormal ST segment changes (3.2%). Further cardiovascular examinations were conducted in 23 patients. Eleven subjects underwent exercise stress scintigraphy and 5 showed abnormal transient perfusion defects. Seven subjects underwent coronary angiography and 4 showed significant one-vessel coronary arterial stenosis. In 3 subjects, antianginal medications were prescribed. In 5 patients, repeated exercise stress test revealed normal results. Exercise duration, peak heart rate, and peak systolic blood pressure did not differ between Group A and Group N. Body mass index and resting systolic blood pressure was significantly higher in Group A than Group N. Resting diastolic pressure, serum total cholesterol, HDL cholesterol, triglyceride, uric acid, and smoking habit did not differ between the two groups. The number of coronary risk factors did not differ between the two groups. Those with more than 2 risk factors were 41.4% in Group A and 29.3% in Group N (p=0.26). In conclusion, exercise stress test as a screening procedure should be applied to healthy men over 50 years of age.