환경독성물질에 의한 폭로는 세포내 DNA의 수복과정에 영향을 미쳐 돌연변이나 암을 유발할 수 있다. 독성물질에 의해 유도된 DNA의 비정상 수복효과를 판단하기 위하여.in vivo에서 MNNG 또는 Benzo(a)pyrene을 투여하고 in vitro에서 Bleomycin을 처리하여 나타나는 염색체이상효과를 관찰하였다. 실험결과, MNNG를 투여 후 Bleomycin을 처리하였을 때 염색체이상의 상승효과가 나타났다. 한편, Benzo(a)pyrene 투여 후 Bleomycin을 처리하였을 패는 높은 농도에서 염색체이상의 상승효과가 나타났다. 이같은 결과는 MNNG나 Benzo(a)pyrene 같은 유전독성물질들이 in vivo에서 세포내 비정상 DNA수복을 일으킬 수 있으며, 이러한 작용은 관련 유전독성물질의 염색체손상성에 무관하며 투여용량에 의존되는 것으로 판단된다.

In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.

To detect the mutation in a given sequence, there are variety of methods developed by use of the gel electrophoresis. One of the methods, TGGE (Temperature Gradient Gel Electrophoresis), is a popular technique because it can detect mutations in DNA fragment with ease and at low cost. This study used 200 bp BamHI-digested DNA fragment containing the human $\varepsilon$-globin promoter which was mutated[$\varepsilon$ F1*(-141), GATA- I*(-163), and GATA-1* & $\varepsilon$F1]. This BamHI-digested DNA fragment was directly used to detect the mutated DNA fragment on 50% denaturant gel with temperature gradient of 45$^{\circ}C$ through $53^{\circ}C$. In agreement with the theoretical result of MELTSCAN program (Brossette and Wallet, 1994) the mobilities of mutated DNA fragments were shown to be nearly distinguished on the temperature gradient gel. In contrast to the above result the heteroduplex analysis under the temperature gradient condition was shown to detect the mutated DNA fragments through the heteroduplex formation between strands of mutated DNA and wild-type DNA.

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by YH1226, a cephalosporin antibiotic regardless of metabolic activation, while positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 25% and 10%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1226 at 500, 250, 125 mg/kg by i.p. once. After 24 hours, animals were sacrificed and evaluated for the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1226 did not induce microunclei in bone marrow of ddY male mice.

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.

Epigallocatechin gallate (EGCG) was reported to exert weak cytotoxicity against normal healthy cells such as C3H10T1/2 cells, but profound inhibitory effects on the initiation or promotion stage of chemical carcinogenesis in mammary gland, blood and mouse skin. This study was carried out to develop antitumor agents with weak side effects and strong antitumor activity. Human skin melanoma cells (HBT 69) and human oral epitheloid carcinoma cells (OCL 17) were cultured in RPMI-1640 media containing 10% fetal bovine serum, antibiotic, and fungizone. After incubation for 24 hrs, the cells were treated with various amounts of (EGCG) for 48 hrs. The growth inhibitory effects of EGCG in human oral epitheloid carcinoma cells were evaluated by the 3- (4,5-djmethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), neutral red (NR), and sulforhodamine B protein (SRB) assays of colorimetric methods. The light microscopic study was also carried out to observe morphological changes of the treated cells. These results obtained were as follows; 1. Significantly inhibitory effects of EGCG against cultured human oral epithelioid carcinoma cells. 2. Significantly inhibitory effects against cultured human skin melanoma cells treated with 50 $\mu$M EGCG, but decreased inhibitory effects in 100 $\mu$M EGCG. 3. Degenerative changes against cultured human oral epitheloid carcinoma cells. 4. Degenerative changes against human skin melanoma cells treated with 50 UM EGCG, but recovered degenerative changes in 100 $\mu$M EGCG.

In the present study, we have evaluated cytotoxic effects of Taraxaci Herba extract in human oral epitheloid carcinoma cells. An antitumor activity was measured by colorimetric assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and sulforhodamine protein B (SRB). The light microscopic study showed morphological changes, Ag-NOR (argyrophylic nucleolar organizer region) number and PAS positive reaction or the treated cells. These results obtained are as follows : MTT and SRB quantities were significantly decreased in cultured KB cells treated with 10$^{-2}$ /mg/ml and 10$^{-3}$ /mg/ml concentrations. The number of Ag-NORs were significantly decreased in cultured KB cells treated with 10$^{-2}$ /mg/ml and 10$^{-3}$ /mg/ml concentrations and the rate of Ag-NORs was shifted to left side (one Ag-Nounucleus was increased and five Ag-NORs/nucleus were decreased) by the high concentration. PAS reaction of cultured KB cells treated with 10$^{-2}$ /mg/ml and 10$^{-3}$ /mg/ml concentrations was negative. These results suggest that Taraxaci Herba retains a potential antitumor activity.

Fluorscence in situ hybridization with chromosome-specific probe has been shown to be a valid and rapid method for detection of chromosome rearrangements induced by chemical and physical agents. This method is useful for quantifying structural aberrations, expecially for stable ones, such as translocation and insertion, which are difficult to detect with conventional method in human lymphocyte. In order to use the FISH method as a biodosimeter for monitoring human population exposed to various chemical and physical agent, baseline level of chromosome rearragement was established. Blood from forty four healthy adults were collected and analysed with whole chromosome-specific probes by human chromosome 1,2 and 4. The frequencies of stable translocation were 2.45 per 100 cell equivalent and those of insertion, color juction, acentric and dicentric were 0.32, 3.28, 0.23 and 0.27 per 100 cell equivalent respectively. The frequencies of chromosome rearragements increased with age in both sexes except for dicenrics. From above result, stable aberrations accumulate with age and it may reflect integrated lifetime exposure of adverse environment.

본 연구는 돌연변이원인 자외선과 ethyl methanesulfonate(EMS) 그리고 bleomycin(BLM)을 전처리한 HeLa 세포에서 세포막에 존재하는 glycoconiugates에 미치는 이들 돌연변이원의 효과를 밝히기 위하여 세포생존 실험법과 Lectin cytochemistry법으로 조사하였다. 1 mM EMS를 전처리한 후 10 mM EMS를 처리한 군의 세포생존율은 10 mM EMS를 단독처리한 군의 세포생존율 보다 더 높았다. 그리고 10 mM EMS 단독처리군 보다 1 mM EMS를 전처 리 한 후 10 mM EMS를 처리한 군에서 Wheat germ agglutinin (WGA)은 더욱 강한 양성반응을 보였다. 반면에 succinylated wheat germ agglutinin (SWGA)는 10 mM EMS 단독처리군과 1 mM EMS를 전처리한 후 10mM EMS를 처리한 군에서 차이가 없었다. 이상의 결과들을 종합해 볼 때, HeLa세포에서 EMS에 대한 획득된 저항성은 다내약제성 또는 적응반응과 관련되는 원형질막의 sialic acid를 포함한 glycoconiugates와 관계 될 것으로 추측된다.

To evaluate the genotoxicity of SKP-450, an antihypertensive agent the in vitro reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the Reverse mutation test, SKP-450 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 with and without metabolic activation. In the chromosome aberration assay using CHL cells, there was no increased incidence of structural and numerical aberrations with and without metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice at 30 hours after treatment with SKP-450 by p.o once. The results showed no increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice treated with SKP-450.

To evaluate the genotoxicity of CKD-602, an anticancer agent the in viかo reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the reverse mutation assay, CKD-602 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535, and TA 1537 strains with and without metabolic activation. In the chromosome aberration test using CHL cells, there was an increased incidence of structural aberrations induced by CKD-602 without metabolic activation during 24 and 48 hours, but CKD-602 did not induce chromosome aberration with metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice. At 24 hours after treatment with CED-602 by i.p. once, there was an increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice.