Sumati V. Bhide

Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice.

The anticarcinogenic effect of dietary turmeric on benzo[a]pyrene-(BP) induced forestomach neoplasia and 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis in female Swiss mice was evaluated. To further elucidate the mechanism of antineoplastic action of turmeric, its effect on the hepatic cytochrome b5, cytochrome P-450, glutathione, and glutathione S-transferase activities was studied in female Swiss mice. Turmeric (2% or 5%) in the diet significantly inhibited the BP-induced forestomach tumors, and this response was dose and time dependent. The 2% turmeric diet significantly suppressed DMBA-induced skin tumors in mice. The 5% turmeric diet for seven consecutive days resulted in a 38% decrease in the hepatic cytochrome b5 and cytochrome P-450 levels. Glutathione content was increased by 12%, and the glutathione S-transferase activity was enhanced by 32% in the liver. Our results document a protective effect of turmeric on BP-induced forestomach and DMBA-induced skin tumors in mice.

Protective role of aqueous turmeric extract against mutagenicity of direct-acting carcinogens as well as Benzo[a]pyrene-induced genotoxicity and carcinogenicity

SummaryTurmeric (Curcuma longa Linn.) has been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of an aqueous turmeric extract (AqTE) and its constituents, curcumin-free aqueous turmeric extract (CFAqTE) and curcumin, using theSalmonella typhimurium mutagenicity assay and the bone marrow micronucleus test in female Swiss mice. AqTE exhibited antimutagenic activity against direct-acting mutagens, 4-nitro-O-phenylenediamine and 1-methyl-3-nitro-1-nitrosoguanidine, in strains TA 98 and TA 100 respectively. Both AqTE and CFAqTE inhibited the mutagenicity of benzo[a]pyrene in the two strains in the presence of Aroclor-1254-induced rat liver homogenate. The inhibition in both studies was dose-dependent. Administration of AqTE, CFAqTE and curcumin at a dose of 3 mg/animal 18 h prior to i.p. benzo[a]-pyrene injection (250 mg/kg) significantly inhibited bone marrow micronuclei formation in female Swiss mice by 43%, 76%, and 65% respectively. Furthermore, the incidence and multiplicity of forestomach tumours induced by benzo[a]pyrene (1 mg/animal, twice weekly, p.o. for 4 weeks) in female Swiss mice were significantly inhibited by AqTE, CFAqTE and curcumin given 2 weeks before, during and after the carcinogen treatment. These data indicate that the protection against genomic damage by turmeric extract and its components tested could be necessary for some aspects of its cancer chemoprevention.

Correlation of mutagenicity and tumorigenicity of betel quid and its ingredients

The mutagenic activity of betel quid and its ingredients was determined using Salmonella typhimurium tester strains TA 100, TA 1535, TA 98, and TA 1538, both in the presence and absence of S9 mixture. Aqueous extracts of betel quid (BQ), betel quid with tobacco (BQT), and betel nut (BN) were mutagenic in strain TA 100. Aqueous extract of betel leaf (BL) was not mutagenic in any of the four strains. Arecoline and arecaidine, which are major alkaloids present in BN, were mutagenic in all four tester strains. Tumorigenicity studies in Swiss mice given the above constituents showed that BN and BQ induced lung tumors (47% and 26%, respectively). However, when BN was fed with BL, tumorigenicity was lowered to 38%. BL alone was not tumorigenic. Thus, the mutagenicity of betel quid and its ingredients is correlated with tumorigenicity.

Nonmutagenicity of curcumin and its antimutagenic action versus chili and capsaicin

Turmeric, which is one of the commonly used spices in Indian cooking, was tested for mutagenicity using the Ames test. The alcoholic extract of fresh or dried turmeric, its principal components, and pyrolyzed turmeric powder and curcumin were tested for mutagenicity in Salmonella typhimurium strains with and without metabolic activation. None of these were mutagenic in all the tester strains. Chilies (which are used with turmeric powder) and their principal alkaloid capsaicin were mutagenic in the TA 98 with S9 mixture. We tested curcumin, which is the principal component of turmeric, for its antimutagenic effect. It showed dose-dependent decreases in mutagenicity of chili extract and capsaicin. Also, we compared the antimutagenicity of curcumin with other known antioxidants, including BHA, vitamins E and C, and vegetable oils. These all showed dose-dependent decreases in mutagenicity of chili extract and capsaicin. These studies show that although there are few mutagenic principles in Indian food, there is still quite a large number of antimutagenic principles in the Indian diet that will modulate the activity of environmental mutagens.

Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products

SummaryThe natural plant products turmeric, β-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of β-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors.

Perinatal carcinogenicity of isoniazid (INH) in swiss mice

SummaryTumorigenicity of isoniazid (INH) and hydrazine sulfate (HS) was studied in male and virgin Swiss mice. The INH and HS induced 50% und 84% lung tumors in males and 67% and 72% in females, respectively. Both chemicals induced lung tumors in animals of the F1 generation that were exposed to INH or HS during intrauterine life, lactation, and in the postweaning period. Surprisingly, the F2 generation from these F1 animals, which were exposed to INH only during gestation and lactation, showed earlier and much higher tumor incidence than the parent generation.

Transplacental passage of isoniazid (INH) and its interaction with fetal tissues of mice

When INH was administered orally or intraperitoneally to pregnant female mice, the concentrations of acetyl INH and acetyl hydrazines did not vary significantly in circulating blood and in amniotic fluid. However, the concentration of INH in the amniotic fluid was significantly higher than that observed in the serum. Autoradiographic studies using 14C-labelled INH revealed that INH crosses the placental barrier and grains can be observed in lung and liver tissues of the fetus. Studies on interaction of 14C-labelled INH with nucleic acids clearly demonstrated that significant amounts of radioactivity were present in all the macromolecules of the whole embryo as well as in those isolated from fetal lung and liver tissues.