KWON, O. S. SCHMUED, L. C. and LSIKKER, W. JR. Neurotoxiciligy. objectives of this study were to test the hypothesis that fumonisin $B_1$ ($FB_1$) alters sphinganine (Sa) levels and myelin synthesis in the central nervous system of developing rats. $FB_1$ (subcutaneous, 0. 4 or 0. 8 mg/kg/day) from postnatal days (PND) 3 to PND 12 resulted in a significantly increased in the brain of rats given 0. 8 mg $FB_1$/kg/day. To confirm the effect of limited nutrition on changes in the Sa levels and myelinogenesis, rats given 0.8mg $FB_1$/kg/day or treated by limited nutrition (temporary removal from dam during postnatal period) were compared to those in saline controls. Sa levels and Sa/So ratios were compared to those in saline in the 0.8 $FB_1$-treated, 3'-phosphohydrolase (CNP) activities were decreased significantly in both nutritionally limited and $FB_1$-exposed rats. These data indicate that sphingolipid metabolism in the central nervous system of develiping rats is vulnerable to $FB_1$ exposure. The hypomyelination associated with $FB_1$-treatment may be mediated by limited nutrition.

Taxol is used as cancer therapeutic agent. It has been known as weak posotive of chromosome aberration assay in vitro in our previous results (Ryu et al., 1996) and potent clastogens in the mouse bone marrow micronucleus (Tinwell and Ashby, 1994). We performed microgel electrophoresis to determine the effect of taxol and it's precursor 10-deacetyl baccatin III(DAB) on DNA. Microgel electrophoresis is useful, rapid, simple, visual, and sensitive technique for measuring DNA breakage and repair mechanisms in mammalian 근ells. The range of concentration used for taxol were 854, 427, 213.5, 106.8, 53.4 Ug/ml, for DAB 910 ,455, 227.5 U9/ml, Cell viability always exceed 85%. We analyzed the results by using the special software of image analyzer for this comet assay (Komet 3.0). By using this image analyzer software , we can get the result as the tail moment ((mean of tail length - mean of head lengh) x tail%DNA/100). A slight increase in DNA migration was observed for taxol at the concentration of 854 Ug/m4 in the absence of S9 mixture. No increased DNA migration was observed after treatment with DAB.

We performed chromosomal aberration assay in Chinese Hamster Lung (CHL) cells in vitro to evaluate theclastogenicity of 11 synthetic chemicals which were listed in Toxicity Evaluation Program of Ministry of Environment of Republic of Korea in 1996. All of the chemicals were carried out MTT assay to determine the 50% cell growth inhibition concentration. All compounds were tested with and without metabolic activation system. Benzoyl chloride revealed positive result at $43\;\mu\textrm{g}/m{\ell}$ in the presence of metabolic activation system, and at 30.8, 61.5 and $123\;\mu\textrm{g}/m{\ell}$ in the absence of metabolic activation system. And p-phenoxy ethanol was observed as positive with the metabolic activation system, but negative without metabolic activation system. Especially 2-propyn-l-ol showed high frequency of pulverization and showed critical difference of cytotoxicity between with and without S9 mixture. Pulverizatiuon is not included in the frequency of structural aberration in our criteria. Dicyclopentadiene, methacrylic acid, aa-dimethylbenzyl hydroperoxide, benzylbutyl phthalate, and p-chlorophenal were revealed negative results.esults.

Transgenic animal and cell line models which are recently developed in toxicology field combined with molecular biological technique, are powerful tools for studying of mutation in vivo and in vitro, respectively. The Big Blue mutagenesis assay system is one of the most widely used transgenic systems. Especially, for the study of direct acting mutagens, Big Blue cell line is very useful and powerful to evaluate mutagenicity because the mutation frequency and mutationspectrlun showed no distinct differences between cell line and animal. The Big Blue cell lines carry stably integrated copies of lambda shuttle vector containing lac I gene as a mutational target. These lambda shuttle vectors are useful for various mutagenesis related studies in eukaryotic system due to their ability to be exposed mutagen and then transfer a suitable target DNA sequence to it convenient organism for analysis. We tried to assess the mutagenic effect of 4-NQO with Big Blue cell line. After the treatment of 4-NQO, genomic DNA was isolated and lambda shuttle vector was packaged by in Vitro packaging and then these were plated on bacterial host in the presence of X-gal to screen mutation in the lac I. We determined MF as a ratio of blue plaques versus colorless plaques and now undergoing the mutation spectrum of 4-NQO in lac J gene sequence.

The cytotoxicological effect of Bt 1-endotoxin, well-known as a bioinsecticide, was investigated on ion channel of insect cell lines. This study attempted to evaluted the specificity by simple experiment to measure the cell swelling using lepidopteran cell lines in isotonic solution containing only one cation. Cell swelling was stimulated in KCI-sucrose isotonic solution as well as TC-100 media containg in solubilized crystal 5-endotoxin. It suggested that the cell swelling by Bt toxin have a relation to K+ channel. The cell swelling may be due to the stimulation K+ influx and simultaneously the penetration of H2O induced by Bt toxin, because the stimulation of swelling was observed with the solubilized toxin in KCI-sucrose isotonic solution, but not in sucrose isotonic solution. Moreover the specific K+ channel blocker, such as 4-arnjnopyrimidine(4-AP) and ouabain, showed the significant effect on the cell swelling induced by Bt toxin. The increasement of the cell swelling induced by 4-AP suggested to be caused by the block of K+ efflux through K+ leak channels. The inhibition of cell swelling by ouabain, which is the well-known inhibitor of Na+, K+-ATPase, suggested to be due to decreasement of K+ influx following diminishment of Na+, K+-ATPase activities.

최근 가장 관심이 집중되고 있는 음용수중의 미량오염물질로는 인위적으로 첨가되는 소독제(disi octant)로 인한 소독부산물(disinfection by-products: DBPs)을 들 수 있다. 1970년대부터 염소소독시 수중의 유기오염물길과 반응하여 발암성물질 과 돌연변이 물질이 다수 함유되어 있는 클로로포름(chloform)을 포함한 트리할로메탄(Trih리omethane: THMs)의 생성이 발견되었으며 이로 인한 건강상의 영향이 지속적으로 보고되고 있다. 염소소독시 780가지 이상의 화합물이 염소와 휴믹산(humic acids)과의 반응에 의해 생성되며, 이중 대부분이 할로겐 화합물로 알려져 있다. 염소 소독부산물로는 인체발암력을 지니고 있는 트리할로메탄(THMs) 이외에도 할로아세틱산(Haloaceticacids: HAAs), 할로아세토나이트릴(Haloacetbnitriles: HANs)등이 주 생성물질인 것으로 알려져 있으나 우러나라의 원수특성에 따른 소독부산물의 생성능 (Formation potential)에 대한 연구가 미흡한 실정이다. 본 연구에서는 우리나라 주요 4대강(한강, 대청호, 영산강, 낙동강)의 원수를 실험실내에서 염소처리하여 생성되는 소독부산물의 생성농과 pH, 체류시간 등의 조건에 따라 생성능을 조사하였다. 각 화합물은 추출 및 농축과정을 거친 후 GC/MSD를 사용하여 물질을 확인한 후 할로겐화합물에 민감한 GC/ECD를 사용하여 시료를 분석하였다. pH와 시간, 원수중의 유기물 함량이 소독부산물의 생성에 많은 영향을 미치는 것으로 나타났다. THMs은 알칼리에서, HAAs의 경우는 약산성에서 접촉시간이 증가할수록 높은 생성능을 보였고, HANs의 경우는 급속히 생성했다가 시간이 경과함에 따라 소멸하며 약산성에서 높은 생성능을 보임을 알 수 있었다, 강별로는 낙동강에서 THMs파 HANs의 생성능이 비교적 높았고, 영산강에서는 HAAs의 생성능이 높았다. 각 원수의 특성에 따른 생성능을 파악함으로써 생성능 저감방안을 마련하며, 소독 부산물질의 인체노출평가에 따른 위해성평가를 통해 관리기준을 설정해야 할 것이다.