Chemoprevention refers to the use of non-toxic chemical agents to prevent the neoplastic development by inhibiting, delaying, or reversing a multi-stage carcinogenesis. The primary goal of chemoprevention research is to identify or produce effective agents and strategies for clinical trials for applications to normal or high risk human populations. A large number of compounds have been tested for their possible chemopreventive activities, and it is of interest to note that many of them are naturally occurring substances. Thus, a variety of plant and vegetable constituents, particularly those included in our daily diet, have been found to possess substantial protective properties against experimental carcinogenesis. These substances, collectively known as dietary phytochemicals, exert their chemopreventive effects by influencing specific step(s) of multi-stage carcinogenesis: some inhibit metabolic activation or enhance detoxification of carcinogens, others interfere with covalent interactions between ultimate eloctrophilic carcinogens and the target cell DNA and still others may exert anti-promoting or anti-progressing effects. Mechanism-based interventions by use of safe dietary phytochemicals may provide one of the most practical and promising cancer chemopreventive strategies.

By far, the largest known preventable cause of cancer is cigarette smoking. The percentage of cancer deaths in Korea due to tobacco is still increasing. Smoking cigarette at an early age has become more common among women. Tobacco consumption is related causally to cancer to the lung, mouth, larynx, esophagus, bladder, kidney, uterine cervix, and pancreas. Recently, several studies demonstrated that there is very strong correlation between cigarette smoking and p53 mutations in lung cancer, head and neck cancer, and bladder cancer. The recent findings of cigarette smoking and cancer, p53 and bcl-2 mutations, adverse effects of smoking on the effects of radiotherapy, and benefits of quitting will be discussed.

Transgenic animal and cell line models which are recently developed and used in toxicology fields combined with molecular biological technique, are powerful tools to study the mechanism of mutation in vivo and in vitro, respectively. Transgenic models, which have exogenous DNA incorporated into their genome, carry recoverable shuttle vector containing reporter genes to assess endogenous effects or alteration in specific genes related to disease processes. The lac I and lac Z gnee most widely used as a mutational target in transgenic systems. The assay is performed by treatment with putative mutagenic agents, isolation of genomic DNA from cells or tissues, exposure the isolated DNA to in vitro packaging extract, plating and sequencing. The results from these processes provide not only mutant frequency as quantitative evaluation but also mutational spectrum as qualitative evaluation of various agents. Therefore we introduce and review the principle, detailed procedure and application of transgenic mutagenesis assay system in toxicology fields especially in mutagenesis and carcinogenesis.

Anticarcinogenic activity of astaxanthin-containing egg yolks (designate AEY) was investigated for 7,12-dimethylbenz[a]anthracene (DMBA)-induced two stage mouse epidermal carcinogenesis. Female ICR mouse (6-7 weeks of age) were house in a humidity-and-temperature-controlled facility and subjected to feed and water ad libitum. AEY (10 mg/0.2 ml acetone) was painted on the back of mice 7 days, 3 days and 5 min before DMBA treatment (50 nmole/0.2 ml acetone). One week later after DMBA treatment, 6 ${\mu}g$ tetradecanoyl 12-phorbol 13-O-acetate (TPA) dissolved in 0.2 ml acetone was applied on the mouse twice weekly over a period of 22 weeks. No sample was given to control mice. Control egg yolk (CEY) and astaxanthin-containing oil (designate AO) from Phaffia rhodozyma were used as positive controls. Mouse treated with AEY exhibited 10 tumors per mouse whereas control mouse exhibited 15 tumors per mouse, the fact that 33% reduction of tumor per mouse by AEY treatment. Tumor incidence was also reduced to 15% by AEY treatment when compared to that of control group. Such effects were also seen in CEY and AO treatment groups, but leaser extent. AO gave reduction of food intake and body weights relative to those of AEY and CEY, indicating toxicity of AO. These results suggest that AEY exhibits anticarcinogenic activity for DMBA-induced mouse epidermal carcinogenesis.

Antimutagenic activity of Saururus chinesis (Lour.) Bail was investigated for food-borne mutagens using S. typhimurium TA98. Methanol extract from Saururus Chinesis (Lour.) Bail was fractionated into hexane, chloroform, ethylacetate and butanol fractions, followed by determination of antimutagenic activity for food-borne mutagenic heterogenic amines (HCA). The hexane fraction exhibited a strong antimutagenic activity for 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQ), 2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyroid[4,3-b]indole acetate (Trp-2-A); however its fraction rather enhanced the bacterial mutagenicity of 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinozaline (4,8-diMeIQx) and 2-amino-3,7,8-trimethyl-3H-imidazo[4,5-f]quinoxline (7,8-diMeIQx). Active principle in the fraction was found to be two major compounds (${\gamma}$-crene B and epi-bicyclosesquiphellandrane) and 6 minor compounds (${\delta}$-caryophyllene, ${\gamma}$-elemene, ${\beta}$-cabebene, ${\delta}$-cadinene, ${\delta}$-selinene, and patchoulene). Modulation effect for the mutagenic activity of the food-borne mutagenic HCA by the fraction might be derived from a cumulative effect of each individual compounds. Hence, this hexane fraction might be use to reduce the production of mutagenic HCA during cooking process of protein-rich foods.

It is previously reported that 6-paradol can induce prolonged analgesia in experimental animals. In order to investigate the mutagenicity of 6-paradol, Ames Samonella/microsome plate assay was carried out with Salmonella typhimurium strains, TA 98, TA 100, TA 1535 and TA 1538, 6-Paradol was nonmutagenic in Salmonella typhimurium with and without rat liver microsomal activation. The rec assay with Bacillus substilis strains H 17 $rec^+$ and M 45 $rec^+$ was carried out ot test 6-paradol and other compounds (1-3 mg/disc) for DNA damaging activity, 6-Paradol was also nonmutagenic in DNA damaging activity. The relative size of the inhibition zone for 6-paradol was smaller than that of capsaicin. We have also determined the pathological effects of this compound on the various tissues of rats after administrating(i.p.) with increasing doses of 4, 8, 12, 16 mg/kg at 2 hour intervals and found no significant changes in terms of histology.

In the present study, we have evaluated cytotoxic effects of the chloroform soluble fraction of the methanolic extract of Perilla frutescens in human oral epitheloid carcinoma cells. The light microscopic study showed morphological changes of the treated cells. Cell membrane damaging activity was measured by the lactate dehydrogenase (LDH) assay and disruptions in cell organelles were determined by 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), neutral red (NR) and sulforhodamine protein B (SRB) of colorimetric assay. These results suggest that Perilla frutescens retains a potential antitumor activity.

굴(Oester)껍질에 은 이온을 도입해 개발한 수질 정화제 Ag-Os의 복귀 돌연변이원성을 관찰하기 위하여, Salmonella typhymurium TA 1535, TA 1537, TA 98, TA 100 이용하였고, DAN-손상여부를 관찰하기 위하여 Bacillus Subtils H-17($Rec^+$)와 H-45($Rec^-$)을 이용하였다. Ag-Os에 의한 복귀 돌연변이는 관찰되지 않았고, 이는 S9을 첨가시에도 같은 현상을 나타내었다. Rec-assay에 의한 DNA 손상도 관찰되지 않은 결과로 미루어, 수질 정화제 Ag-Os는 본 시험 조건에서 변이원성을 보이지 않음을 확인하였다.