To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of ［S-35］-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of ［S-35］-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of ［S-35］-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of ［S-35］-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

Gly460Trp polymorphism of a-adducin gene has been reported to be associated with hypertension in some populations, and we, therefore, attempted to replicate this finding in Korean population. There were no significant differences in allele and genotype frequencies of Gly460Trp polymorphism in Korean normotensives and hypertensives, respectively. The meta-analysis revealed that the Mantel-Haenszel estimate of the odds ratio across the studies was 1.17 (95%CI 1.04-1.31), and that there was significant evidence against homogeneity of the odds ratio among the studies included (Breslow-Day test = 27.34, df = 9, p = 0.001). Although the meta- analysis appeared in favour of association between the Gly4601tf polymorphism of $\alpha$-adducin gene and hypertension, there was the considerable heterogeneity among the studies and the evidence is also rather borderline. Further comprehensive approaches are needed to resolve this debatable issue.

In human U-937 cell exposed to ${\gamma}$-irradiation and $H_2O$$_2$, the level of mRNA efrpression in ceruloplasmin gene was measured by using comparative RT.PCR (reverse transcriptase-polymerase chain reaction). At the normal growth condition, the level of ceruloplasmin transcript was estimated as 8.2% and 0.0068% of hprt (hypoxantine phosphoribosyl transferase) transcript and of $\beta$-actin transcript, respectively. In U-937 cells exposed to a dose of 100 rad ${\gamma}$-irradiation, the level of ceruloplasmin transcript was increased about 2.7 and 1.6 fold compared to un-treated cell by using compensation with the levels of hprt and $\beta$-actin transcript. By contrast, the expression of ceruloplasmin gene in U-937 cells exposed to $H_2O$$_2$(50 $\mu$M, 24 h), was shown no significant difference compared to un-treated cell. These results indicated that the expression system of ceruloplasmin gene may react only some specific oxygen species, such as reactive oxygen species induced by ${\gamma}$-irradiation.

The single cell gel electrophoresis (comet) assay is one of the useful tools for the study of genetic damage in humans exposed to environmental mutagens and carcinogens. This study was undertaken to evaluate the status of DNA damage in peripheral lymphocytes depending on their sex, age, smoking habits, and other factors in normal healthy Korean population. The 99 volunteers included in the study and out of these, 36 volunteers were smoker and 63 volunteers were non-smoker aged between 20-59 years. All individual answered a questionnaire that assessed their general information including smoking habits and the extent of the environmental tobacco smoke (ETS) exposure, and blood samples were obtained. There was a statistically significant difference in the extent of DNA damage between smoker and non-smoker (p<0.001). A significant difference was also observed between male and female (p<0.001) and amongst the different group of age (p<0.005), however, correlation analysis showed that only smoking habit was a significant factor for DNA damage. No significant effect of smoking duration, number of cigarettes smoking a day, SPY (smoke pack years) in smokers and environmental tobacco smoke exposure in non-smokers on the status of DNA damage was observed.

Benzene is a widespread human carcinogen, inducing leukemia and hematotoxicity. Exposure to benzene metabolites has been shown to cause genetic damage, including aneusomy and chromosome aberrations. Fluorescence in situ hybridization(FISH) procedure was used to determine if the benzene metabolite, 1, 2, 4-benzenetriol(BT), hydroquinone(HQ) and trans, trans-muconic acid(t,t-MA) induced specific chromosomal change in HL-60 cells. Treatment with BT, HQ and t,t-MA resulted in the induction of monosomy 8 and 21 in HL-60 cells in a dose-dependent manner. All of these metabolites also induced trisomy 8 and 21, but no correlation between frequencies of trisomy and concentration was found. Translocations between chromosome 8 and another unidentified chromosome ［t(8:\ulcorner)］, and between chromosome 21 and another unidentified chromosome ［t(8:21)］ were found. However, translocation between chromosome 8 and 21 ［t(8:21)］ was not found. Results indicate that the benzene metabolites, BT, HQ and t,t-MA, induce chromosome specific numerical and structural aberrations, and the fluorescence in situ hybridization (FISH) approach may be a useful and powerful technique for detection of aneuploidy.

Nowadays a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms are developed and manufactured with safety evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. This study was carried out to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice. In this study, doses which we determined to expose to mice were 40 cigarettes for 6 hours a day to mice in single dose and 20 (high dose), 10 (middle dose) and 5 cigarettes (low dose) a day for 28 days in repeated dose inhalation toxicity, in vivo chromosome aberration test and micronucleus test. The particulate substances from H menthol herbal cigarettes also were gathered and used in the Salmonella typhimurium/microsome assay (Salmonella test; Ames test). We could find neither significant changes between control and treatment groups nor dose-response effects of test material at all except serum Ca level of female middle dose treatment group in repeated dose inhalation toxicity test. In conclusion, H menthol herbal cigarettes, when applied clinically intended dose we used, might not show any toxic and/or mutagenic effect.

AG6O, the complex of acriflavine and guanosine, has been shown to possess the synergistic antitumorigenic activity in the previous paper (J. Pharm. Pharmacol. 1997, 49:216). In this study, we have investigated the genotoxic properties of AG60 using in vitro and in vivo system such as Ames bacterial reversion test, chromosomal aberration assay and micronucleus assay. In Ames reverse mutation test, AG60 treatment at the dose range up to 250 $\mu\textrm{g}$/plate caused the dose-independent random induction of the mutagenic colony formation in S. typhimurium TA98, TA100, TA1537, and E. coli WP2uvrA, while any mutagenic effect of AG60 wasn't observed in S. typhimurium TA1535. Any significant chromosomal aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells incubated with PBS or AG60 at the concentrations of 2.5, 5, 10 $\mu\textrm{g}$/$m\ell$ for 24 hours without but even with 59 metabolic activation system for 6 hours. In vivo ICR mice, the intramuscular injection of AG60 at the doses of 7.15, 14.3, and 28.6 mg/kg did not induce the frequency of micronucleus formation. However, mitomycin C, as one of the positive controls at the dose of 2 mg/kg caused the 8.4% induction in the frequency of micronucleus and 24% increase in the chromosomal aberration.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to exert detrimental toxicities on various organ systems including reproductive, cardiovascular, nervous, or dermal system. Immunomodulatory effects of TCDD is thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation and activation, which were demonstrated using experimental animals, whereas immunotoxicity in human has not been investigated well. This study was proceeded to evaluate general immunologic spectrum of the Korean Vietnam War veterans exposed to TCDD during their operation, and compare with that of the non-exposed control subjects with similar age. Regarding composition and quantity, immune cells in peripheral blood collected from the TCDD-exposed was not much different from those of the control except decreased red blood cell, hemoglobin and hematocrit level. Furthermore, plasma IgG2, G3, and G4 isotype distribution was similar between two groups, but IgG1 level was significantly lowered in the TCDD-exposed, indicating a TCDD-mediated functional alteration of B cells. Significantly enhanced level of IgE in plasma, a hallmark of dermal or respiratory allergic response, was also observed in the TCDD-exposed compared with that of the control. Elevated generation of IL-4 and IL-10 was resulted from in vitro stimulation of T cells with PMA plus ionomycin or PHA, respectively, from the TCDD-exposed in comparison to those of the control, suggesting a skewed type-2 response. In addition, the level of IFN${\gamma}$, a multifunctional cytokine for T cell-mediated immunity, was lowered in the TCDD-exposed with upregulation of tumor necrosis factor $\alpha$. The present study suggests that TCDD exposure disturbs immunohomeostasis in humans observed as an aberrant plasma IgE and IgG1 levels and dysregulation of T cell activities.

To evaluate the modifying effect of Kwao Kreu, Pueraria mirifica (PM) well-known as a rejuvenating folk medicine from Thailand, peri- and post-natal studies were carried out in rats. PM extract was administered to pregnant Sprague Dawley (SD) rats by oral gavage from gestation 6 (GD 6) to postnatal day 21 (PND 21). The amount of administered in this study was 0.042, 0.42 and 4.2 mg/kg/day, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. Treatment related changes in body weight, food consumption and lactation of dams were not observed. F1 fetuses in external abnormality, physical development, reflex/sensory functions and behavioral development were not found. No adults and F1 fetuses in organ weight was found with the exception of vagina and uterus of F1 fetuses. The results showed that PM extract, up to 4.2 mg, had no adverse effects on the peri- and post-natal development of rats. Therefore, PM extract has no adverse effects on peri- and post-natal development of rats.