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Asian Pacific Journal of Cancer... 2007Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental...
Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental animals. Presently we have evaluated the inhibitory effects of potentized homeopathic preparations against N'-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in rats as well as 3-methylcholanthrene-induced sarcomas in mice. We have used Ruta, Hydrastis, Lycopodium and Thuja, which are commonly employed in homeopathy for treating cancer. Administration of NDEA in rats resulted in tumor induction in the liver and elevated marker enzymes such as gamma-glutamyl transpeptidase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase in the serum and in liver. Concomitant administration of homeopathic drugs retarded the tumor growth and significantly reduced the elevated marker enzymes level as revealed by morphological, biochemical and histopathological evaluation. Out of the four drugs studied, Ruta 200c showed maximum inhibition of liver tumor development. Ruta 200c and phosphorus 1M were found to reduce the incidence of 3-methylcholanthrene-induced sarcomas and also increase the life span of mice harboring the tumours. These studies demonstrate that homeopathic drugs, at ultra low doses, may be able to decrease tumor induction by carcinogen administration. At present we do not know the mechanisms of action of these drugs useful against carcinogenesis.
Topics: Animals; Drugs, Investigational; Female; Homeopathy; Liver; Liver Neoplasms, Experimental; Methylcholanthrene; Rats; Rats, Wistar; Ruta; Sarcoma, Experimental
PubMed: 17477781
DOI: No ID Found -
The Journal of Biological Chemistry Nov 1963
Topics: Anti-Bacterial Agents; Antimetabolites; Azo Compounds; Enzyme Induction; Enzyme Inhibitors; Hydrolases; Liver; Methylcholanthrene; Orphenadrine; Pharmacology; Phenobarbital; Phenylbutazone; Piperazines; Puromycin; Rats; Research
PubMed: 14109205
DOI: No ID Found -
The Journal of Toxicological Sciences Aug 1983Intrarenal distribution of cytochrome P-450 (P-450) was investigated with different segments of isolated single nephrons from rabbits and rats by using a new ultra-micro...
Intrarenal distribution of cytochrome P-450 (P-450) was investigated with different segments of isolated single nephrons from rabbits and rats by using a new ultra-micro method of P-450 determination. In both animals, P-450 was localized only in the proximal tubule. Other segments such as the glomerulus, the loop of Henle, the distal tubule, and the collecting tubule possessed no P-450 at all. Within the proximal tubule, the straight portion (S2 and/or S3 segments) revealed a higher specific content of P-450 than the convoluted one. An inducer of P-450, 3, 4-benzo(a)pyrene increased the P-450 of a definite portion (second 3 mm from the glomerulus) almost doubly in rabbits. In rats, both 3-methylcholanthrene (3MC) and 48 hr starvation (Fast) induced P-450, but only the later increased laurate-omega-hydroxylation. P-450 in the proximal convoluted and straight tubules was induced separately by Fast and 3MC, respectively. These results indicate that renal mixed function oxidase should be confined to the proximal tubule and that, like the liver, multiple forms of renal P-450 should exist in the different proximal segments.
Topics: Animals; Benzo(a)pyrene; Benzopyrenes; Cytochrome P-450 Enzyme System; Enzyme Induction; Fasting; Hydroxylation; In Vitro Techniques; Kidney Tubules, Proximal; Laurates; Male; Methylcholanthrene; Microsomes; Nephrons; Phenobarbital; Rabbits; Rats
PubMed: 6319725
DOI: 10.2131/jts.8.165 -
Proceedings of the National Academy of... Oct 1976Aryl 4-monooxygenase [aniline, reduced-flavoprotein:oxygen oxidoreductase (4-hydroxylating); EC 1.14.14.1] activity was searched for and found in homogenates of aorta...
Aryl 4-monooxygenase [aniline, reduced-flavoprotein:oxygen oxidoreductase (4-hydroxylating); EC 1.14.14.1] activity was searched for and found in homogenates of aorta walls from rabbits, rhesus monkeys, and humans. Specific activities were comparable to activities observed in several other extrahepatic tissues of rabbits and monkeys and in epidermal tissues from mice, but were one to two orders of magnitude lower than those observed in corresponding preparations of hepatic tissues. Cytochrome P-450 also could be detected in low concentrations in microsomal fractions of aortic wall homogenates. The monooxygenase activity found in the aorta could play a significant role in the etiology and pathogenesis of atherosclerosis in humans by catalyzing the conversion of environmental promutagens to mutagenic initiators and/or cytotoxic factors, thus leading to development of benign, smooth muscle tumors of the inner lining of artery walls.
Topics: Animals; Aorta; Arteriosclerosis; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 Enzyme System; Enzyme Induction; Haplorhini; Humans; Macaca mulatta; Male; Methylcholanthrene; Rabbits
PubMed: 824648
DOI: 10.1073/pnas.73.10.3723 -
European Journal of Biochemistry Aug 1974
Topics: Animals; Binding Sites; Carbon Radioisotopes; Cell Membrane; Enzyme Activation; Esters; Glucuronates; Glucuronosyltransferase; Hexosyltransferases; In Vitro Techniques; Kinetics; Liver; Methylcholanthrene; Microsomes, Liver; Naphthols; Organ Size; Perfusion; Phenobarbital; Proteins; Rats; Sulfuric Acids; Surface-Active Agents; Uridine Diphosphate Sugars
PubMed: 4212510
DOI: No ID Found -
Environmental Health Perspectives Mar 1989Cell culture systems are instrumental in elucidating regulation of normal function and mechanisms of its perturbation by toxic substances. To this end, three...
Cell culture systems are instrumental in elucidating regulation of normal function and mechanisms of its perturbation by toxic substances. To this end, three applications of epithelial cells cultured with 3T3 feeder layer support are described. First, treatment of the premalignant human epidermal keratinocyte line SCC-12F2 with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate suppressed cell growth and differentiation. This agent produced a biphasic growth response greatly inhibiting cell growth at 1 to 10 nM, but much less above 100 nM. Expression of the differentiated functions involucrin and transglutaminase was found to be inhibited markedly at concentrations above 10 nM. Second, 3-methylcholanthrene toxicity was surveyed in a variety of rat epithelial cell types. The two most sensitive to growth inhibition were epidermal and mammary epithelial cells, while those from bladder, prostate, thyroid, and endometrium were insensitive to growth inhibition. Great differences were evident even among those cells derived from stratified squamous epithelia (epidermal, esophageal, vaginal, forestomach) despite their expression of aryl hydrocarbon hydroxylase activities to similar degrees. Finally, expression of estrogen receptors in rat endometrial cells was shown to be stimulated by the cAMP-elevating agent forskolin. Maximal stimulation of 3- to 6-fold occurred in 6 hr, compatible with a requirement for protein synthesis. Although expressing keratinocyte character (transglutaminase activity and envelope forming ability), the cells thus retain some hormonal character that may be modulated by cAMP-dependent kinase activity. Pursuit of such results will aid in understanding differences in response among cell types and species, in elucidating mechanisms of action of known toxic substances and, ultimately, in predicting toxicity of less well understood agents.
Topics: Animals; Cell Differentiation; Cell Line; Cells, Cultured; Colforsin; Endometrium; Epidermal Cells; Epithelial Cells; Female; Humans; In Vitro Techniques; Keratins; Methylcholanthrene; Mice; Rats; Receptors, Estrogen; Tetradecanoylphorbol Acetate
PubMed: 2466642
DOI: 10.1289/ehp.8980239 -
The Journal of Biological Chemistry Mar 1975Multiple forms of liver microsomal cytochrome P-450 isolated from immature male rats pretreated with phenobarbital or 3-methylcholanthrene are described. Afraction of...
Multiple forms of liver microsomal cytochrome P-450 isolated from immature male rats pretreated with phenobarbital or 3-methylcholanthrene are described. Afraction of low specific content (Fraction A. 1.7 TO 4.0 nmol of cytochrome P-450 per mg of protein) and a fraction substantially purified (Fraction B, 9.0 TO 11.0 NMOL of cytochrome P-450 per mg of protein) are obtained by DEAE-cellulose chromatography of a partially purified cytochrome P-450 preparation in the presence of Emulgen 911. Shifts in the absorption maxima in the CO-reduced and ethyl isocyanide difference spectra are observed in the fractions derived from 3-methylcholanthrene-treated rats. The fractions derived from phenobarbital-treated rats exhibit different 455:430 ratios and pH intercepts in the ethyl isocyanide difference spectra. The absolute oxidized spectra and n-octylamine binding spectra at room temperature and EPR analysis at the temperature of liquid helium characterize all the fractions, except the Fraction A from 3-methylcholanthrene-treated rats, as low spin ferric hemeproteins. The A hemeprotein fractions from both 3-methylcholanthrene- and phenobarbital-treated rats have poor catalytic activity for the metabolism of benzphentamine and 3,4-benzo-[a]pyrene in comparison to the B hemeprotein fractions which may be due to the presence of a high concentration of Emulgen 911 in the A fractions. However, the presence of Emulgen 911 cannot account for the spectral differences among the fractions.
Topics: Amines; Animals; Benzopyrenes; Benzphetamine; Chromatography, DEAE-Cellulose; Cyanides; Cytochrome P-450 Enzyme System; Hemeproteins; Male; Methylcholanthrene; Microsomes, Liver; Phenobarbital; Protein Binding; Protein Conformation; Rats; Spectrophotometry
PubMed: 1117002
DOI: No ID Found -
Environmental Toxicology May 2016Metal-based nanoparticles (NPs), are currently used in many application fields including consumer products, pharmaceuticals, and biomedical treatments. In spite to their...
Metal-based nanoparticles (NPs), are currently used in many application fields including consumer products, pharmaceuticals, and biomedical treatments. In spite to their wide applications, an in-depth study of their potential toxic effects is still lacking. The aim of the present research was to investigate the potential initiator or promoter-like activity of different metallic NPs such as gold, iron, cobalt, and cerium using the Balb/3T3 two-stage transformation assay. The results indicated that all the selected metallic NPs, except for cobalt, when used as initiators did not induce any transformation in Balb/3T3 cell line. Moreover, Au and Fe3 O4 NPs, when used in place of the tumor promoter treatment TPA, increased significantly the number of Foci/dish as compared to the MCA treatment alone. The number of Foci/dish was 2.6 for Au NPs and 2.13 for Fe3 O4 ones, similar to those obtained by the positive control treatment (MCA + TPA), whereas 1.27 for MCA treatment alone. On the contrary, CeO2 NPs did not show any difference in the number of Foci/dish, as compared to MCA alone, but it decreased the number of foci by 65% in comparison to the positive control (MCA + TPA). As expected, cobalt NPs showed an increased cytotoxicity and only a few surviving cells were found at the time of analysis showing a number of Foci/dish of 0.13. For the first time, our data clearly showed that Au and Fe3 O4 NPs act as promoters in the two stage transformational assay, suggesting the importance to fully investigate the NPs carcinogenic potential with different models.
Topics: 3T3 Cells; Animals; Carcinogens; Cell Survival; Cell Transformation, Neoplastic; Cerium; Ferrosoferric Oxide; Gold; Metal Nanoparticles; Methylcholanthrene; Mice; Mice, Inbred BALB C; Microscopy, Electron; Tetradecanoylphorbol Acetate
PubMed: 25358123
DOI: 10.1002/tox.22063 -
The Journal of Biological Chemistry Jan 1982
Comparative Study
Effects of 3-methylcholanthrene, beta-naphthoflavone, and phenobarbital on the 3-methylcholanthrene-inducible isozyme of cytochrome P-450 within centrilobular, midzonal, and periportal hepatocytes.
Topics: Animals; Antigen-Antibody Complex; Benzoflavones; Cytochrome P-450 Enzyme System; Enzyme Induction; Flavonoids; Immune Sera; Isoenzymes; Male; Methylcholanthrene; Microscopy, Fluorescence; Microsomes, Liver; Organ Specificity; Phenobarbital; Rats; beta-Naphthoflavone
PubMed: 7054190
DOI: No ID Found -
The Journal of Biological Chemistry Nov 1986We have isolated cDNA clones of the mRNA for rat UDP-glucuronosyltransferase that catalyzes the glucuronidation of 4-nitrophenol, by using synthetic oligonucleotides as...
We have isolated cDNA clones of the mRNA for rat UDP-glucuronosyltransferase that catalyzes the glucuronidation of 4-nitrophenol, by using synthetic oligonucleotides as hybridization probes. The complete nucleotide sequence of the 1,927-base pairs cDNA insert has been determined. With untranslated sequences of 124 and 216 base pairs in the 5'- and 3'-terminal regions, respectively, the cDNA insert contained 1,587 base pairs that encode a complete primary structure of a putative precursor form of 4-nitrophenol UDP-glucuronosyltransferase with a calculated molecular weight of 60,114. The cDNA sequence also indicates the presence of 25 amino acids preceding the sequence determined by microsequence of the isolated protein. This extrapeptide, for the most part, consists of hydrophobic amino acids which are characteristic of the signal peptides as found for secretory proteins and most transmembrane proteins. Furthermore, the deduced amino acid sequence contains a putative halt transfer signal of a hydrophobic segment (residues 487-510), which is flanked on both sides by the peptide segments of highly charged amino acid residues (residues 463-486 and 511-529). These features are consistent with the properties of transmembrane proteins. Specific cDNA probes were used to analyze the induction of the enzyme in rat tissues by treatment with 3-methylcholanthrene. RNA blot analysis showed that 3-methylcholanthrene increased 10- to 15-fold the amount of hybridizable mRNA in liver. The livers and kidneys from 3-methylcholanthrene-treated rats were found to contain almost the same amount of hybridizable mRNA, although the basal level in the kidney was much higher than that of the liver, and the amounts in the lung were much lower than that of the liver and kidney.
Topics: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA; Enzyme Induction; Female; Glucuronosyltransferase; Isoenzymes; Methylcholanthrene; Nucleic Acid Hybridization; Oligonucleotides; Peptide Fragments; RNA, Messenger; Rats; Rats, Inbred Strains
PubMed: 3096993
DOI: No ID Found