• The Korean Journal of Zoology
• /
• 제26권3호
• /
• pp.155-170
• /
• 1983

The primary concern has been focused on the response and adaptation of mouse fibroblast tumor cells to heat-shock in the level of membrane surface proteins, using two labeling techniques, lactoperoxidase-catalyzed iodination and galactose oxidase-sodium borohydride. Cells arrested in $G_1$ phase exhibited the highest level of LETS protein and high molecular proteins than did cells passing through $G_1/S, S, G_2$ and M, and unsynchronized cells. Confluent cells were found to show an increase in 125K proteins and a decrease in 130K and 100K proteins selectively. The adaptation processes of tumor cells after heat-shock were observed. All the proteins above 80K were reduced immediately after heat-shock, whereas 70K protein increased markedly 24 hours after heat-shock. The 70K protein and high molecular proteins returned to normal level in 48 hours. The 70K protein was found to be trypsin-sensitive and was similarly labeled by galactose-oxidase as well as by lactoperoxidase. It was, therefore, concluded that 70K protein is glycoprotein located on the surface membrane and might be the HSP 70. Possible function of heat-shock protein on the surface membrane and the relation of this protein to differential heat-sensitivity of tumor cells are discussed.

• Toxicological Research
• /
• 제23권4호
• /
• pp.405-413
• /
• 2007

This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

• Toxicological Research
• /
• 제23권4호
• /
• pp.391-403
• /
• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Toxicological Research
• /
• 제23권4호
• /
• pp.353-362
• /
• 2007

Deoxynivalenol (DON) is a common food borne mycotoxin and occurs predominantly in grains such as wheat, barley, oats, etc. DON induces systemic health problems such as loss of appetite, emesis and diarrhea in both human and farm animals. Reliable diagnostic parameters for DON intoxication are needed to prevent deep health impact. In order to establish useful diagnostic parameters, we investigated clinical signs, hematological values, serum biochemical values, gross-, histo- and toxico-pathological findings in B6C3F1 male mice after oral administration of DON (0.83, 2.5 and 7.5 mg/kg) for 8 days. Body weight gain was significantly decreased at the highest dose of DON. Anorexia, ataxia, for crudness and lack of vigor were observed at the highest dose DON group. In hematological values, the numbers of WBC and platelets and hemoglobin content were reduced with decreased neutrophil and monocytes by 7.5 mg/kg DON. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged in a dose-dependent manner and the content of fibrinogen was elevated at high dose of DON. Of serum biochemical values, total protein, globulin, BUN, cholesterol and test-osterone were reduced but total bilirubin and albumin/globulin ratio increased. The enzyme activity of alkaline phosphatase was decreased while that of alanine aminotransferase was elevated. Relative organ weights of thymus, seminal vesicle/prostate and testes were dose-dependently reduced but those of liver and left adrenal gland increased with dose dependency. As for pathological findings, atrophy of thymus, seminal vesicle/prostate and testes and submucosal edema and ulceration in stomach and depletion of lymphocytes in thymus cortex were observed. In conclusion, these clinical, hematological, blood biochemical and patholgical parameters obtained in the present studies can be used for diagnosis of DON-mycotoxicosis, especially, low WBC, platelets, protein, BUN and testosterone and delayed prothrombin time can be available as for reliable diagnostic parameters.

• Toxicological Research
• /
• 제23권4호
• /
• pp.321-330
• /
• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• Toxicological Research
• /
• 제23권4호
• /
• pp.331-339
• /
• 2007

Titanium or titanium alloy is a widely used implant material according to its certified biocompatibility, sufficient strength and ready availability. The purpose of this study was to evaluate the relative biocompatibility of titanium and titanium alloy specimens (Ti-29Nb-13Ta, TiNb and Ti-6Al-4V, Ti64) using in vivo and in vitro methods. For in vivo experiment, the specimens were implanted in the abdominal subcutaneous region of female mice for 2 and 4 weeks. The reaction of connective tissue to specimens was evaluated histologically. The specimens were encapsulated by fibrous connective tissue consisting of fibroblast, fibrocyte and other cells including neutrophil, macrophage, giant multinucleated cell and unidentified cells. Some newly formed blood vessels were located in the fibrous capsule surrounding the implant. Cell types and the thickness of fibrous capsules were examined quantitatively. Most of cell types located in the fibrous capsule were fibroblasts and fibrocytes. The average thickness of fibrous capsules for the TiNb specimens was much thinner than that of the titanium alloy, Ti64. The thickness of the fibrous capsule around all titanium specimens decreased at 4 weeks compared to 2 weeks post-implantation. The biocompatibility of titanium and titanium alloy specimens were also investigated in in vitro method using alkaline phosphatase from MG-63 cells. Alkaline phosphatase activity of the TiNb specimen showed higher activity than the titanium alloy, Ti64. In conclusion, the TiNb alloy with thin capsule thickness in vivo and high alkaline phosphatase activity in vitro will be of considerable use in biomedical applications.

• Toxicological Research
• /
• 제24권4호
• /
• pp.263-271
• /
• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Toxicological Research
• /
• 제24권4호
• /
• pp.273-280
• /
• 2008

The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

• Toxicological Research
• /
• 제24권4호
• /
• pp.307-314
• /
• 2008

The present study was carried out to investigate the potential adverse effects of 1,3-dichloro-2-propanol on pregnant dams after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The tested chemical was administered orally to pregnant rats at dose levels of 0, 10, 30, or 90 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights, and Caesarean section findings were examined. In the 90 mg/kg group, decreases in the body weight gain and food consumption, and increases in the weights of liver and adrenal glands were observed. Serum biochemical investigations revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol (CHO), triglyceride (TG), alkaline phosphatase (ALP), and bilirubin (BIL) and decreases in glucose (GLU), albumin (ALB) and total protein (TP). In the 30 mg/kg group, a decrease in the food consumption and an increase in the liver weight were observed. Serum biochemical investigation also showed increases in CHO and TG and a decrease in glucose. Since there were no signs of maternal toxicity in the 10 mg/kg group, it is considered to be the no-observed-adverse-effect level (NOAEL) of 1,3-dichloro-2-propanol. It is concluded that successive oral administration of 1,3-dichloro- 2-propanol to pregnant rats for 14 days may cause significant toxicities in body weight and liver at a dose rate ${\geq}$ 30 mg/kg/day.

• Toxicological Research
• /
• 제24권2호
• /
• pp.119-127
• /
• 2008

The objectives of this study were to examine the lung injury and inflammation caused by manual metal arc stainless steel(MMA-SS) welding fume inhalation and to evaluate the recovery process. Sprague-Dawley rats were exposed to MMA-SS welding fumes for 2 h per day in a whole-body exposure chamber, with a total suspended particulate(TSP) concentration of $51.4{\pm}2.8mg/m^3$(low dose) or $84.6{\pm}2.9mg/m^3$(high dose) for 30 days. The animals were sacrificed after 30 days of exposure as well as after a 30-day recovery period. To assess the inflammatory or injury responses, cellular and biochemical parameters as well as cytokines were assayed in the bronchoalveolar lavage fluid(BALF). MMA-SS welding fume exposure led to a significant elevation in the number of alveolar macrophages(AM) and polymorphonuclear cells(PMN). Additionary, the values of $\beta$-n-acetyl glucosaminidase($\beta$-NAG) and lactate dehydrogenase(LDH) in the BALF were increased in the exposed group when compared to controls. After 30 days of recovery from exposure, a significant reduction in inflammatory parameters of BALF was observed between the exposed and recovered groups. Slight, but significant elevations were noted in the number of AM and PMN in the recovered groups, and AM that had been ingested fume particles still remain in the lungs. In conclusion, these results indicated that welding fumes induced inflammatory responses and cytotoxicity in the lungs of exposed rats. Fume particles were not fully cleared from lungs even after a 30-day recovery period.