The clastogenic activity of capsaicin, a major pungent and irritating constituent of hot chili pepper, was evaluated in cultured human lymphocytes. Capsaicin (125, 250, and 500 $\mu$M) caused cytogenetic damage as determined by increased frequency of chromosome/chromatid aberrations compared to the solvent control. The mitotic indices were also decreased in a concentration-related manner in capsaicin-treated cells. Moreover, capsaicin suppressed [$^3$]thymidine incorporation into lymphocytes. The clastogenicity and cytotoxicity of capsaicin towards human lymphocytes were evident without an external metabolic activation system. Taken together, these findings suggest that capsaicin is a genotoxic agent and may thus represent a potential health hazard in humans.

Effects of hyperthermia on the induction of DNA single strand breaks and replication inhibition were studied in bleomycin-treated CHO-K$_1$ cells by alkaline elution and alkaline sucrose gradient sedimentation. Bleomycin-induced DNA single strand breaks of DNA were dose-and time-dependently increased, and these strand breaks of DNA were gradually rejoined as post-incubation time passed. Treatment with hyperthermia alone did not affect the induction of DNA single strand breaks. However, pre-exposure of cells to hyperthermia followed by bleomycin treatment greatly increased the single strand breaks, and also reduced the rejoining processes of bleomycin-induced DNA single strand breaks. Bleomycin selectively inhibited the replicon initiation. The combined treatment with hyperthermia and bleomycin markedly potentiated the nonspecific inhibition of replication.

The adaptive response and cross-adaptive response to sister chromatid exchanges (SCEs) and DNA single-strand breaks (SSBs) in Chinese hamster ovary (CHO)-K$_1$ cells treated with ultraviolet radiation (UV), ethyl methanesuffonate (EMS), or bleomycin (BLM) were investigated. Two assays were used in this study; SCEs and alkaline elution. The pretreatment with low conditioning dose of 2 mM EMS or 1 J/m$^2$ UV decreased the yield of SCEs induced by subsequent treatment with 8 mM EMS, 5 J/m$^2$ UV or 5 $\mu$g/ml BLM. And the pretreatment with low conditioning dose of 1 $\mu$g/ml BLM decreased the yield of SCEs induced by subsequent treatment with 5 $\mu$g/ml BLM or 5 J/m$^2$ UV. The rejoining of DNA SSBs in cells subsequently treated with 2 J/m$^2$ UV, 50 mM EMS or 400 $\mu$g/ml BLM is higher than that only treated with 2 J/m$^2$ UV, 50 mM EMS or 400 $\mu$g/ml BLM. These results suggest that there are the adaptive response and cross-adaptive response to SCEs, and is the adaptive response to the rejoining of DNA SSBs in CHO cells.

The effects of DNA polymerase $\beta$ on the somatic chromosome mutations and mitotic recombinations were investigated using the transgenic Drosophila beating chimetic gene consisting of a promoter region of Drosophila actin 5C gene and rat DNA polymerase $\beta$. For detecting the somatic chromosome mutations and mitotic recombinations, the heterozygous (mwh/+) strains possessing or lacking transgene poi 13 were used. The spontaneous frequency of small mwh spots, due to deletion or nondisjunction etc., in the non-transgenic w strain and the transgenic p[pol $\beta$]-130 strain was 0.351 and 0.606, respectively. The spontaneous frequency (0.063) of large mwh spots, arises mostly from somatic recombination between the centromere and the locus mwh, in the transgenic p[pol $\beta$]-130 strain was about three times higher than that (0.021) of the non-transgenic w strain. The mutant clone frequencies of small and large mwh spots induced by N-methyl-N'-nitro-N-nitrosoguanidine and ethyl methanesulfonate in the transformant p[pol $\beta$]-130 were higher than those in the host strain w. The present results suggest that rat DNA polymerase $\beta$ participate at least in the somatic chromosome mutations and mitotic recombination processes.

A method was developed to detect total mutagenicity of fried fish for S. typhimurium TA98, using Ames assay. Method described herein circumvented problems associated with the sample preparation for Ames assay, i.e., a multi-purification step of sample and interference with solvent residuals. Experiment A, the best method developed in the present study, consisted of two important steps: pH adjustment of the aqueous sample solution from fried fish samples to remove impurities, and simultaneous distillation extraction (SDE) for partially purified samples to remove volatile compounds from solvents. The procedure and results were described as below. Fillet of gizzard shad (Konosirus punctatus) fish sample fried for 10 min each side on the temperature-controlled fry-pan (210$\circ$C) was homogenized in an aqueous acidic solution (pH 2) with a homogenizer, followed by filtration through Celite. The tiltrate (pH 2), removed some impurities by extraction with chloroform:methanol (2:1, v/v) mixture, was adjusted pH to 10 and then centrifuged to remove precipitate. The ethylacetate extract from the tiltrate of pH 10 was rotoevaporated and purified by SDE apparatus for 2 hours. Experiment A revealed significantly higher revertants (1928 per 25 g fried sample) than other Experiment (B, C, or D) tested. Experiment A gave good results in the mutagenicity test of fried fish sample with few purification steps using only 25 g fried sample and 650 ml of solvents; and thus this method could be a useful tool for the screening the mutagenicity or antimutagenicity of other foods as well.

Bacterial mutagenicity of shellfish or canned products of red-muscle fish affected by hot-airdry processings and/or during storages was investigated by Ames preincubation method. Mussel (Mytilus edulis) and surf clam (Tapes japonica) dried under either 40$\circ$C, 50$\circ$C or 60$\circ$C until remained about 25 % water content was stored at 4$\circ$C or 25$\circ$C for 6 months. Commercially available canned product of pacific saury (Cololabis saira) and mackerel saury (Scotnberjaponicus), whose producer or date of manufacture was identical each other, was stored at 25$\circ$C for 6 months. Mutagenic substances from sample (25 g dry weight) were extracted and purified for mutagenicity assay against S. typhitnurium TA98 by the simultaneous distillation extraction (SDE) method (Lee et al. 1955). Mutagenicity of sample was expressed number of revertant per 25 g dry sample. Number of revertant from unheated mussel sample was appeared to be 135, relative to 22 from unheated surf clam sample. Mutagenicity of both shellfish was strongly affected by heat treatment, but a lesser extent by storage conditions, even at 25$\circ$C for 6 months. Revertants of the mussel sample dried at 40$\circ$C, 50$\circ$C, or 60$\circ$C was found to be 227, 779, and 883, respectively. Similar, but lower, mutagenicity was observed from the sample of surf clam dried at 40$\circ$C, 50$\circ$C, or 60$\circ$C than mussel. Mutagenicity of canned pacific saury and mackerel samples was not influenced by storage conditions. Number of revertant from pacific saury was 175 which was relatively higher than 5 from mackerel. Mutagenicity of fresh pacific saury and mackerel samples was significantly higher than that of their counterparts from canned products. These results indicate that mutagenicity of the shellfish was affected by heat treatment (40$\circ$C, 50$\circ$C, or 60$\circ$C) used for drying process, but not much by storage for 6 months at 4$\circ$C or 25$\circ$C and the mutagenicity of canned products of red-muscle fish was not influenced by storage, even at 25$\circ$C for 6 months.

In order to evaluate the cytotoxicity of lead in cultures of Balb/c mouse 3T3 cell line, various cytotoxic assays were carried out after expose cells to various concentrations of lead nitrate. Cytotoxic assays using this study were included NR assay, MTT assay, measurement of LDH and protein, synthetic rate of DNA and UDS. Intrace!!ular Ca$^{2+}$ level was also measured. Light and electron microscopic studies were done for morphological changes of lead-treated cell cultures. The results were as follows; 1. The absorbances of NR and MTT were decreased dose-dependently, and NR, and MTT, values of lead nitrate were 3.4 mM and 1.5 mM, respectively. 2. Amount of LDH released into the medium was increased in dose-dependently and LDH activity at 5 mM concentration of lead nitrate was increased to 335 % of control. 3. Amount of total protein was decreased dose-dependently, and which was half of control at 2 mM concentration of lead nitrate. 4. The synthetic rate of DNA was decreased dose-dependently, and also which was remarkably decreased at 3 mM and 5 mM concentrations of lead nitrate. 5. The synthetic rate of UDS was increased at 1 mM concentration of lead nitrate, but which was remarkably decreased at 3 mM and 5 mM concentrations of lead nitrate. 6. Intrace!lular Ca$^{2+}$ level was remarkably increased at 1 mM concentration of lead nitrate, compared with control. 7. In light microscopy, number of cells and processes were decreased according to the increase of dosage of lead nitrate. Electron microscopic findings showed that many vacuoles and cisternal dilatation of rough endoplasmic reticulum were seen in the cytoplasm at 1 mM concentration of lead nittale. From the above results, high dosage treatment of lead nitrate (>3 mM) damaged genetic malerials and it also showed cytotoxicity in mouse 3T3 cell line cultures by injury of cell organelles and Ca$^{2+}$ channel.

Air suspedned particulates are the most serious factor among air pollutants in Seoul and their extracts have been revealed to be pulmonary carcinogenes. Air particulates were collected at a site representative of the high traffic area of Seoul from December 1993 to May 1994. Polycyclic aromatic hydrocarbons (PAHs) and nitroarenes in organic extracts of air particulates were determined by gas chromatography and mutagenicity of particle extracts was evaluated by the pre-incubation procedure with Salmonella typhirnurium TA98 and TA 98NR. The average concentration of total suspended particulates and inhalable (less than 10 $\mu$m) particulates were 169.63 $\mu g/m^3$, 141.92 $\mu g/m^3$, respectively. The relative contribution of organic matters was highest in neutral fraction and was lowest in basic fraction. Among identified 20 PAHs, the level of PAHs with 4-benzen ring i.e., pyrene, benzo(a)anthracene and chrysene were much higher than the PAHs with higher ring numbers. The mutagenicity of air particulates was much higher in the presence of rat liver microsomai fraction (S9 mixture) than that observed in its absence, which indicates that air particulates contained both direct and indirect mutagens. Nitroarenes in this study were not almost detected but mutagenicity of their fraction was higher. These results are represent to research for the identification of nitroarenes in the forward study.

For studying the effect of different dietary fats on carcinogenesis, fatty acid composition of membrane and lipid peroxidation were measured. Male Sprague-Dawley rats were fed on diet containing 15%(w/w) beef tallow or soybean oil. A single dose of 50 mg 2-AAF/kg B.W. was injected i.p. in each diet group 10 times. Rats were sacrifled after 1, 5, 10, and 15 weeks from the first injection. By 2-AAF injection, !ipid peroxidation increased slightly compared to control group. The rats fed on different fats had similar MDA production and those fed on soybean oil had slightly higher free radical concentration measured by ESR. In young rats, iipid peroxidation level was high and hydroxy radical production was higher in soybean oil group than in beef tallow group. With age, the lipid peroxidation values were decreased initially then increased. The fatty acid composition in microsomal membrane was reflected by dietary fatty acid composition. In soybean oil group, monoenoic acid was lower and polyunsaturated fatty acid was higher than beef tallow group. Linoleic acid contents showed the most discrepancy among groups. By 2-AAF treatment, iinoleic acid content and unsaturation index increased in soybean oil group. But in beef tallow group, there was no difference in fatty acid contents.