Retardation of experimental tumorigenesis and reduction in DNA adducts by turmeric and curcumin.

Turmeric and its active principle curcumin have been extensively investigated for their antimutagenic and antioxidant effects in bacterial and animal systems. Because oral cancers are common in India, an experimental model of 7,12-dimethylbenzanthracene-induced buccal pouch tumors in Syrian Golden hamsters was used to evaluate the tumor retardation effects of turmeric and curcumin. Turmeric and/or curcumin was administered in the diet and/or applied locally for 14 weeks along with 7,12-dimethylbenzanthracene. After the experimental period, the animals were sacrificed and oral pouches were examined for tumor number and size. DNA adducts were estimated by 32P postlabel assay in the cheek pouches. Neoplastic changes were graded by histopathology. The results of the study suggest that turmeric or curcumin in the diet and/or applied locally significantly reduced DNA adducts at the target site. Tumor number and tumor burden were significantly lower (p < 0.05) in the animals that received turmeric in the diet and applied locally. The histopathological examinations suggested that the neoplastic grading was least in the animals fed or painted with curcumin (p < 0.05). The current study demonstrates that turmeric or curcumin administered in the diet or applied as paint may have a plausible chemopreventive effect on oral precancerous lesions.

Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity.

In cancer chemoprevention trials, biomarkers as intermediate end points have gained importance. A variety of biomarkers have been proposed as intermediate end points for upper aerodigestive tract cancers. This study was aimed at studying the frequency of micronucleated cells and carcinogen DNA adducts as indicators of DNA damage and intervention end points in chemoprevention trials. Reverse smokers of chutta (rolled tobacco) from four villages numbering 298 in total were selected. Out of these, 150 were supplemented with four nutrients (vitamin A, riboflavin, zinc and selenium) and 148 controls received placebo, one capsule twice a week for 1 year. Slides of buccal smears were prepared and stained with Fuelgen reaction and counterstained with Fast Green and examined microscopically for the presence of micronucleated cells. Oral cell washings were collected and centrifuged. The DNA adducts were evaluated by the 32P post-labelling assay method. Protein and RNA free DNA (adducted) isolated from the cells was digested with MN/SPD and the DNA adducts isolated by the butanol enrichment procedure. The DNA adducts were identified and quantitated by multidimensional chromatography on PEI-TLC sheets by screen enhanced autoradiography and presented as RAL (relative adduct labelling) values. Both the micronuclei and DNA adducts were significantly elevated in subjects with lesions. At the end of 1 year the frequency of micronuclei decreased significantly (P < 0.001) in the supplemented subjects with or without lesions. The DNA adducts in the supplement group at the end of 1 year also reduced significantly. The adducts decreased by 95% in subjects with all categories of lesions and by 72% in subjects without lesions. No such effects were noted in the placebo group. The two biomarkers investigated in the case study appear to be modifiable by the administration of micronutrient supplements.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of turmeric and curcumin on BP-DNA adducts.

Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention.

In vitro stimulation of microsomal diethyl nitrosamine deethylase activity by vitamin K3 (menadione).

Vitamin K3 (menadione) has been found to stimulate diethyl nitrosamine (DEN)-deethylase activity in rat liver microsomes. The vitamin also takes care of the inhibitory effect of the anaerobic conditions as well as those of cytochrome poisons like sodium azide and sodium cyanide, possibly through production of active oxygen species. The enzyme was also stimulated by H2O2 and SOD and inhibited by catalase, thereby suggesting that H2O2 or some derivatives of it may be the active oxygen species involved in the reaction.

Effects of female sex steroids on concanavalin A-mediated agglutination of hepatocytes from nonregenerating and regenerating rat liver and hepatic tumor marker enzymes.

Effect of treatment of female rats with an oral contraceptive agent (OCA), Ovulen-50, for 7 weeks on agglutination of hepatocytes with concanavalin A (con A) and activities of certain tumor marker enzymes were examined to find out if OCA treatment is related to preneoplastic or neoplastic processes. Hepatocytes from regenerating and nonregenerating livers of control female rats showed negligible agglutination with Con A, whereas hepatocytes from non regenerating but not from the regenerating livers of female rats treated with a combination of 5 micrograms ethinyl estradiol and 100 micrograms ethynodiol diacetate showed agglutination. Of the tumor marker enzymes such as hepatic glucose 6-phosphatase, gamma-glutamyl transpeptidase (gamma-GT), and arginase examined in the liver, only gamma-glutamyl transpeptidase showed a significant increase in activity in the steroid-treated rats. Plasma alkaline phosphatase activity was also higher in the treated animals. However, the magnitude of the changes observed was relatively small and perhaps unrelated to the neoplastic process.

Liver regeneration in oral contraceptive treated female rats--effects of moderate malnutrition.

Treatment of well-nourished female rats with a combination of 5 micrograms ethynyl estradiol and 100 micrograms ethynodiol diacetate, increased the DNA content, 3H thymidine incorporation into DNA and mitotic activity in the non-regenerating liver, but impaired liver regeneration after partial hepatectomy. In rats which were moderately malnourished by feeding 25 percent less calories and 50 percent of recommended allowance for vitamins A and B2, OC treatment had similar stimulatory effect on non-regenerating liver, but did not impair liver regeneration after partial hepatectomy. Analysis of nucleotide bases after hydrolysis of unpolymerized nucleotides and nucleosides revealed significant perturbations due to OC treatment. However, the impaired liver regeneration due to OC treatment of well-nourished rats could not be attributed to diminished availability of bases, particularly thymidine. Data on mitotic index and binucleate cell numbers suggest that besides inhibiting mitosis (DNA duplication), OC treatment of well-nourished rats may also impair partitioning of binucleate cells.

Effect of Ovulen-50(ethynodiol diacetate 1 mg and ethynyloestradiol 0,05 mg) on protein, nucleic acids and nucleases in the rat liver.

Treatment of adult female rats with Ovulen-50 (ethynodiol diacetate 1.0 mg and ethynyloestradiol 0.05 mg--one tenth tablet per day) led to a small but significant fall in total protein, RNA and DNA content of the liver. Alkaline and acid DNAse activity also tended to decline, whereas alkaline RNAase tended to show a marginal rise after twentyfour days of treatment.