Brief introduction of Panax ginseng C.A. Meyer.

For many many thousand years, mankind has been using various plants as nutrient, beverage, cosmetics, dye and medicine to maintain health and to improve quality of life. In Aisa, particularly, Panax ginseng C.A. Meyer is considered to be the most precious plant among herbs, and ginseng has been in the spotlight worldwide. Even in the Western world, where there are greatly advanced research facilities and highly qualified man-power available, and are regarded to be capable of conquering any hard-to-cure ailments, many peoples has recently been reported to use herbal medicine, particularly ginseng. In the present compilation of papers, many scientists contributed papers pertaining to "Chemopreventive effects of ginseng". In order to facilitate the readers understand easier and better, I catalogued this collection as follows: The spiritual nature of ginseng in the Far East, the history of ginseng, nomenclature and geographical distribution of ginseng, and type of ginseng products.

Epidemiological study on cancer prevention by ginseng: are all kinds of cancers preventable by ginseng?

In the light of experimental results, two case-control studies and one cohort study in a population of ginseng cultivation area were conducted to confirm whether ginseng has any anticarcinogenic effect on human cancers. All participants were interviewed using a standardised questionnaire to obtain the information on demographics, cigarette smoking, alcohol consumption and ginseng intake. In 905 pairs case-control study, 62% had a history of ginseng intake compared to 75% of the controls, a statistically significant difference (p<0.01). The odds ratio (OR) for cancer in relation to ginseng intake was 0.56. In extended case-control study with 1987 pairs, the ORs for cancer were 0.37 in fresh ginseng extract users, 0.57 in white ginseng extract users, 0.30 in white ginseng extract users, 0.30 in white ginseng powder users, and 0.20 in red ginseng users. Those who took fresh ginseng slices, fresh ginseng juice, and white ginseng tea, however, did not show decrease in the risk. Overall, the risk decreased as the frequency and duration of ginseng intake increased. With respect to the site of cancer, the ORs for cancers of the lip, oral cavity, pharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, lung and ovary were significantly reduced by ginseng intake. Smokers with ginseng intake showed lower ORs for cancers of lung, lip, oral cavity and pharynx and liver than those without ginseng intake. In 5 yr follow- up cohort study conducted in the ginseng cultivation area, Kangwha-eup, ginseng intakers had significantly lower risk than non-intakers. As for the type of ginseng, cancer risk significantly decreased among intakers of fresh ginseng extract, alone or together with other ginseng preparations. Among 24 red ginseng intakers, no cancer death occurred during the follow-up period. The risk for stomach and lung cancers was significantly reduced by ginseng intake, showing a statistically significant dose-response relationship in each follow-up year. In conclusion, Panax ginseng C.A. Meyer has been established as non-organ specific cancer preventive, having dose response relationship. These results warrant that ginseng extracts and its synthetic derivatives should be examined for their preventive effect on various types of human cancers.

Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds.

The failure to improve the five-year survival rate of cancer patients, from one in three in the 1960s to one in two in the 1970s, stimulated awareness of the importance of primary prevention of cancer. Korean investigators carried out extensive long-term anticarcinogenicity experiments with 2000 newborn mice to investigate whether Panax ginseng C.A. Meyer inhibited carcinogenesis induced by several chemical carcinogens in 1978. There was a 22% decrease (p<0.05) in the incidence of urethane induced lung adenoma by the combined use of red ginseng extract. In the group sacrificed at 56 weeks after the treatment with aflatoxin B1, the incidence of hepatoma significantly decreased to 75% by the addition of red ginseng extract (p<0.05). The result showed that natural products can provide hope for human cancer prevention. By the newly established '9 week medium-term anticarcinogenicity test model of lung tumors in mice' (Yun's model), we confirmed significant anticarcinogenic effects of powders and extracts of the 6- yr-old dried fresh ginseng, 5- and 6-yr old white ginsengs, and 4-, 5-, and 6-yr old red ginseng. We also demonstrated that the anticarcinogencity of ginseng was more prominent in aged or heat treated extracts of ginseng and red ginseng made by steaming. To investigate the active components for cancer prevention, several fractions of 6-yr old fresh ginseng and red ginseng, four semi-synthetic ginsenoside Rh1, Rh2, Rg3 and Rg5, major saponin components in red ginseng, were prepared. Among the ginsenosides, Rg3 and Rg5 showed statistically significant reduction of lung tumor incidence and Rh2 had a tendency of decreasing the incidence. Ginsenoside Rg3, Rg5 and Rh2 were found to be active anticarcinogenic compounds. Rg3, Rg5 and Rh2 are active components in red ginseng, and they prevent cancer either singularly or synergistically.

Panax ginseng--a non-organ-specific cancer preventive?

For the past 50 years, the main weapons in the war against cancer have been early detection and surgical removal, radiotherapy, chemotherapy, and attempts to develop gene therapy. However, the results so far are less than ideal. One strategy now is to switch from therapeutic approaches to prevention of cancer by improving lifestyle and by identifying effective natural products as chemopreventive agents. One promising candidate with cancer-preventive effects that are not specific to any organ is Panax ginseng C A Meyer, a herb with a long medicinal history. Its protective influence against cancer has been shown by extensive preclinical and epidemiological studies, but these effects need to be carefully investigated by scientific clinical trials focusing on the major cancer killers stomach, lung, liver, and colorectal cancer.

The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence.

OBJECTIVE: We have reviewed the potential cancer-preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in Oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-1998) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer-preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

Update from Asia. Asian studies on cancer chemoprevention.

In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long-term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine-week medium-term model using mouse lung tumors (Yun's model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan-specific cancer preventive agent associated with a dose-response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine-week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2-(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum indicum, beta-carotene, and 13-cis retinoic acid do not. This result regarding beta-carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. Subsequently, (-)-epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. Despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo-controlled intervention trials of dietary fiber are under study in Japan. In the past decade, new triterpenoids were isolated from various natural sources, and its biological activities were investigated in Asia. In the late 1970s a comprehensive chemoprevention program was established at the Institute of Materia Medica, Chinese Academy of Medical Sciences. Since then, many retinoid compounds have been synthesized and screened in the search for chemopreventive cancer agents. The National Cancer Institute (USA) and China are jointly engaged in the two-nutrition intervention in Linxian, China. The results of joint study of the general population and of dysplasia in China should stimulate further research to clarify the potential benefits of micronutrient supplements. We need to clarify if there is a connection between the lower rates of cancer mortality in Korea and the frequent consumption of anticarcinogenic vegetables or traditional foods, including ginseng and Ganoderma lucidum. The constituents of the nontoxic stable dietary products promise to be the future hope for conquering cancers in the coming years.

Non-organ specific cancer prevention of ginseng: a prospective study in Korea.

BACKGROUND: A number of studies have reported that increased consumption of natural products reduced the risk of cancer. Our previous case-control studies have shown a significant reduction in the risk of cancer development among those who regularly consumed ginseng. We conducted a prospective cohort study to evaluate the preventive effect of ginseng against cancer on a population residing in a ginseng cultivation area on the basis of the result of case-control studies. METHODS: This study was conducted in Kangwha-eup from August 1987 to December 1992. We studied 4634 people over 40 years old who completed a questionnaire on ginseng intake. In an attempt to obtain detailed information about ginseng intake, we asked them to specify their age at initial intake, their frequency and duration of ginseng intake, the kind of ginseng, etc. Multiple logistic regression was used to estimate relative risks (RR) when controlling simultaneously for covariates. RESULTS: Ginseng consumers had a decreased risk (RR = 0.40, 95% confidence interval [CI] : 0.28-0.56) compared with non-consumers. On the type of ginseng, the RR was 0.31 (95% CI: 0.13-0.74) for fresh ginseng extract consumers and 0.34 (95% CI: 0.20-0.53) for consumers of multiple combinations. There was no cancer death among 24 red ginseng consumers. There was a decreased risk with a rise in the frequency of ginseng intake, showing a dose-response relationship. The RR of ginseng consumers were 0.33 (95% CI: 0.18-0.57) in gastric cancer and 0.30 (95% CI : 0.14-0.65) in lung cancer. Among ginseng preparations, fresh ginseng extract consumers were significantly associated with a decreased risk of gastric cancer (RR = 0.33, 95% CI: 0.12-0.88). CONCLUSIONS: These results strongly suggest that Panax ginseng C.A. Meyer has non-organ specific preventive effect against cancer, providing support for the previous case-control studies.

Saponin contents and anticarcinogenic effects of ginseng depending on types and ages in mice.

AIM: To compare the anticarcinogenic effects of fresh, white, and red ginseng (Panax ginseng C A Meyer) roots and their saponins. METHODS: Lung adenoma in newborn N:GP (S) mice was induced by a subcutaneous injection of benzo(a)pyrene 0.5 mg. After weaning, ginseng powders or extracts were given in the drinking water for 6 wk. In the 9th wk the incidence and multiplicity of lung adenoma were counted. RESULTS: Anticarcinogenic effects were found in 6-year-dried fresh ginseng, 5- and 6-year white ginseng, and 4-, 5-, and 6-year-red ginseng powders. Anticarcinogenic effects were also found in 6-year-dried fresh ginseng, 5- and 6-year-white ginseng, and 4-, 5-, and 6-year-red ginseng extracts. The content of major ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 showed a little higher tendency in fresh or white ginsengs than red ginseng. This tendency was increased as the cultivation ages were increased. But there was no relationship was found between ginsenoside contents and preparation types or cultivation ages. CONCLUSION: Long-cultivated ginseng and red ginseng contain a higher amount of anticarcinogenic components.

Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs.

This study presents the risk of various cancers in relation to ginseng intake based on the data from a case-control study conducted in the Korea Cancer Center Hospital. Ginseng intakers had a decreased risk [odds ratio = 0.50, 95% confidence interval (CI) = 0.44-0.58] for cancer compared with nonintakers. On the type of ginseng, the odds ratios for cancer were 0.37 (95% CI = 0.29-0.46) for fresh ginseng extract intakers, 0.57 (95% CI = 0.48-0.68) for white ginseng extract intakers, 0.30 (95% CI = 0.22-0.41) for white ginseng powder intakers, and 0.20 (95% CI = 0.08-0.50) for red ginseng intakers. Intakers of fresh ginseng slice, fresh ginseng juice, and white ginseng tea, however, showed no decreasing risk. There was a decrease in risk with the rising frequency and duration of ginseng intake, showing a dose-response relationship. On the site of cancer, the odds ratios were 0.47 for cancer of the lip, oral cavity, and pharynx; 0.20 for esophageal cancer; 0.36 for stomach cancer; 0.42 for colorectal cancer; 0.48 for liver cancer; 0.22 for pancreatic cancer; 0.18 for laryngeal cancer; 0.55 for lung cancer; and 0.15 for ovarian cancer. In cancers of the female breast, uterine cervix, urinary bladder, and thyroid gland, however, there was no association with ginseng intake. In cancers of the lung, lip, oral cavity and pharynx, and liver, smokers with ginseng intake showed decreased odds ratios compared with smokers without ginseng intake. These findings support the view that ginseng intakers had a decreased risk for most cancers compared with nonintakers.(ABSTRACT TRUNCATED AT 250 WORDS)

Trial of a new medium-term model using benzo(a)pyrene induced lung tumor in newborn mice.

A new medium-term in vivo model was tried using pulmonary adenoma induced by benzo(a)pyrene (BP) in newborn mice. Both inbred mice such as C57BL/5J, C57BR/cdJ. A/J mice and non inbred N:GP(S) mice were used. Benzo(a)pyrene was injected in the subscapular region of newborn mice within 24 hours after birth at a dose of 0.5 mg and 1 mg per mouse, respectively. After 9 weeks lung tumor induced in N:GP(S) and A/J mice but in the other mice. The dose showing a 50% tumor incidence was found in N:GP(S) mice to be 0.5 mg of BP but the tumor incidence was very high in A/J mice even at 40 micrograms of BP, the lowest dose in this experiment. To verify the utility of this model, ascorbic acid, carrot, beta carotene, soybean lecithin, spinach, Sesamum indicum, Ganoderma lucidum, caffeine, red ginseng extract, fresh ginseng and 13-cis retinoic acid, some of which are known to have anticarcinogenic activity in various animal models, were tried with this system. Ascorbic acid, soybean lecithin, Ganoderma lucidum, caffeine and red ginseng extract showed inhibition of lung tumor incidence, while fresh ginseng, carrot, beta carotene, spinach and 13-cis retinoic acid did not. This result suggested that the 9-week medium-term model using lung tumor induced by 0.5 mg of BP was useful for the screening of cancer preventive agents.

Usefulness of medium-term bioassay determining formations of pulmonary adenoma in NIH(GP) mice for finding anticarcinogenic agents from natural products.

Various long-term bioassay methods have been used to determine the carcinogenicity of chemical substances. Among them, a long-term method developed by Toth (1968), which scores the incidence of pulmonary adenoma formation at 28 to 56 weeks following subcutaneous administration of chemical carcinogens to new-born mice is used widely. This particular long-term bioassay method, while it takes long periods, has proved useful in determining the anticarcinogenic effect of ginseng extracts against the pulmonary adenoma formation inducible with dimethylbenzanthracene, urethane, and aflatoxin B1. More recently, in order to shorten the assay durations to 9 weeks (medium-term), we have modified the existing method by adjusting the doses of carcinogens to be administered to the new-born mice. We have established a modified method in which 40-50% of mice were found to develop pulmonary adenoma 9 weeks after a subcutaneous injection of 0.5 mg/kg to new-born mice of NIH(GP) strain and this modified medium-term bioassay system was found useful in the screening of cancer preventive agents among natural products, such as ginseng and caffeine.

A case-control study of ginseng intake and cancer.

The effect of ginseng consumption on the risk of cancer was investigated by interviewing 905 pairs of cases and controls matched by age, sex, and date of admission to the Korea Cancer Center Hospital, Seoul, Korea. Of the 905 cases 562 (62%) had a history of ginseng intake compared to 674 of the 905 controls (75%) a statistically significant difference (p less than 0.01). The odds ratio (OR) of cancer in relation to ginseng intake was 0.56 (95% confidence interval (CI), 0.45-0.69). Ginseng extract and powder were shown to be more effective than fresh sliced ginseng, the juice, or tea in reducing the OR. Odds ratios for decreasing levels of ginseng intake were 1.00, 0.58, 0.43 and 0.25 for males and 1.00, 0.81, 0.56 and 0.52 for females. A trend test showed a significant decrease in proportion of cancer cases with increasing frequency of intake for males (p less than 10(-5)) as well as for females (p less than 0.05). Chi-square homogeneity tests also confirmed significant differences between cases and controls for both sexes (p less than 10(-3)). The reliability of recall for ginseng use was assessed by interviewing 180 randomly-selected subjects twice using the same questionnaire. The overall agreement in reported ginseng use between the two interviews was 0.85, and the Kappa value was 0.71 (p less than 0.01). These results strongly support the hypothesis of preventive effects of ginseng on cancer suggested by earlier animal studies.

Natural killer and lymphokine-activated killer activities in stomach cancer patients with special emphasis on the effect of 5-fluorouracil, adriamycin and mitomycin-C chemotherapy.

The cytotoxicities of peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells were studied to evaluate the effect of chemotherapy on cellular immunity, in 18 patients with unresectable stomach cancer before and after chemotherapy with 5-fluorouracil, adriamycin and mitomycin-C (FAM), and in 21 healthy volunteers. LAK cells were generated in vitro by culturing PBL with 100 U recombinant human interleukin-2 (rH-IL-2)/ml for 72 h. K562 (human myelogenous leukemia), MKN-45 (human stomach adenocarcinoma) and PC-14 (human pulmonary adenocarcinoma) were used as target cells. The cytotoxicity of PBL to K562 and MKN-45 was suppressed in patients with stomach cancer before chemotherapy, compared with that in healthy volunteers (P less than 0.05). The cytotoxicity of LAK cells was significantly higher to all three cell lines tested than that of PBL in both the healthy volunteers and stomach cancer patients (P less than 0.01); however, a lower level of LAK activity was generated in patients with cancer compared to that in the healthy volunteers. FAM therapy did not suppress the cytotoxicities of PBL and LAK cells. The surface markers of PBL and LAK cells were measured, demonstrating that there was no significant change in the percentage of lymphocytes with CD3+, CD4+, CD8+, CD16+ or CD19+ after chemotherapy. The ratios of CD4+ to CD8+ cells in PBL and LAK cells were also not significantly changed after chemotherapy. In the present study, we have demonstrated that the PBL of stomach cancer were defective in generating LAK activity compared to those of controls, but the LAK activity generated from PBL receiving chemotherapy was similar to that from PBL without chemotherapy in stomach cancer patients.

Enhancement of cytotoxicity of cisplatin in vitro by recombinant human tumor necrosis factor and/or recombinant human interferon-alpha, -beta and -gamma.

This study was conducted to investigate the modulatory effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon (rH-IFN)-alpha, -beta and -gamma, either alone or in combination, on the cytotoxicity of cisplatin, using MTT assay, against MKN-45 (human stomach adenocarcinoma). MKN-45 was resistant to rH-TNF even at doses up to 10(3) U/ml. rH-IFN-gamma inhibited the survival of MKN-45 dose-dependently, while rH-IFN-alpha and -beta did not inhibit the survival of MKN-45 even at the highest concentrations tested (10(4) U/ml). Combination of rH-TNF with rH-IFN-alpha, -beta or -gamma did not significantly inhibit the survival of MKN-45, except for a combination of 10 U/ml of rH-TNF and 10(3) U/ml of rH-IFN-gamma (P less than 0.05). Cisplatin inhibited the survival of MKN-45 dose-dependently. By the simultaneous combination of cisplatin with rH-TNF and/or rH-IFN-alpha, -beta or -gamma, cytotoxicity of cisplatin was enhanced and the combination effects were additive. The effects of rH-TNF and rH-IFN-alpha, -beta and -gamma on the modification of cytotoxicity of cisplatin were evaluated in terms of modification index (MI), demonstrating that rH-TNF, rH-IFN-alpha, -beta and -gamma all augmented the cytotoxicity of cisplatin: MI values at 10(3) U/ml of rH-IFN-alpha, -beta and -gamma were 1.4, 1.4 and 2.3, respectively; those at the same concentrations of rH-IFN-alpha, -beta and -gamma in the presence of 10 U/ml of rH-TNF were 3.6, 2.5 and 5.1, respectively. These results demonstrating that the cytotoxicity of cisplatin was enhanced by rH-TNF and/or rH-IFN-alpha, -beta or -gamma suggest that cancer may be more effectively treated with the combination of cisplatin with these biological response modifiers than with cisplatin alone.

Inhibitory effect of capsaicin on mouse lung tumor development.

The modification potentials of capsaicin on the development of pulmonary adenoma in newborn NIH (GP) mice were examined. Mice were given a single subcutaneous injection of 1 mg of benzo(a)pyrene (BP) or 40 micrograms of 9,10-demethyl-1,2-benzanthracene (DMBA) within 24 hours after birth and then 0.01% capsaicin (CAP) in the diet (Groups 1 and 2) for 6 weeks after weaning. Mice of groups 3, 4, 5 and 6 were given capsaicin, BP, DMBA and vehicle alone. All mice were sacrificed at week 9. Capsaicin caused a significant inhibitory effect on the frequency of tumor-bearing mice (BP-treated group) and the mean number of tumor (DMBA-treated group). The inhibitory activity is most profound in the group of female mice given DMBA combined with capsaicin. These results showed that capsaicin has inhibitory potential in the mouse lung tumor development induced by polycyclic aromatic hydrocarbons (BP and DMBA).

Effect of red ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and benzo(a)pyrene.

It was previously reported that red ginseng extract inhibited carcinogenesis by urethan, DMBA, and aflatoxin B1 [Yun et al: Cancer Detect Prevent 1983; 6:515-25]. In an attempt to investigate the mechanism of the anticarcinogenic effect of ginseng, the natural killer (NK) activity and the incidence of lung adenoma were followed over a period of 48 weeks postinjection with urethan or benzo(a)pyrene. The NK activity was markedly depressed from 4 weeks to 24 weeks after injection of carcinogens. This decreased NK activity was returned to the level of controls by administration of ginseng. At the same time, a lower incidence of lung adenoma was noted following administration of ginseng to urethan-injected mice. However, the lung adenoma induced by benzo(a)pyrene began to occur at 48 weeks in which NK activity had naturally declined to a level too low to be affected by ginseng, and administration of ginseng did not decrease the incidence. In conclusion, these results suggest that the anticarcinogenic effect of ginseng may be related to the augmentation of NK activity.

Anticarcinogenic effect of long-term oral administration of red ginseng on newborn mice exposed to various chemical carcinogens.

This investigation was carried out to evaluate the effects of ginseng in inhibition or prevention of carcinogenesis induced by various chemical carcinogens. Korean red ginseng was administered orally to the newborn mice. 9, 10-Dimethyl-1,2-benzanthracene (DMBA), urethane, and aflatoxin B1 were injected in subscapular region of ICR mice within 24 hr after birth. Controls comprised three groups of ICR newborn mice: normal, (100) ginseng, (200), and vehicle (316). The six experimental groups of ICR newborn mice comprised DMBA (101), DMBA combined with ginseng (103), urethane (94), urethane combined with ginseng (92), aflatoxin B1 (50), and aflatoxin B1 combined with ginseng (47). The mice were autopsied immediately following sacrifice. All major organs were examined grossly and weighed. Histopathological examinations were also made. In the group sacrificed at 48 weeks after the treatment with DMBA (DMBA combined with ginseng extract), the average diameter of the largest lung adenomas decreased by 23%. The incidence of diffuse pulmonary infiltration decreased by 63%, and the average lung weight of male mice decreased by 21%. In the group sacrificed at 28 weeks after the treatment (urethane combined with ginseng), there was a 22% decrease (P less than 0.05) in the incidence of lung adenoma. In the group sacrificed at 56 weeks after birth (aflatoxin B1 combined with ginseng), there were decreases in the incidence of lung adenoma (29%) and hepatoma (75%) (P less than 0.05). These findings indicate that the prolonged administration of Korean red ginseng extract inhibited the incidence and also the proliferation of tumors induced by DMBA, urethane, and aflatoxin B1.