griseofulvin and Cell-Transformation--Neoplastic

Griseofulvin (GF) has been in use for more than 30 years as a pharmaceutical drug in humans for the treatment of dermatomycoses. Animal studies give clear evidence that it causes a variety of acute and chronic toxic effects, including liver and thyroid cancer in rodents, abnormal germ cell maturation, teratogenicity, and embroyotoxicity in various species. No sufficient data from human studies are available at present to exclude a risk in humans: therefore, attempts were made to elucidate the mechanisms responsible for the toxic effects of GF and to address the question whether such effects might occur in humans undergoing GF therapy. It is well documented that GF acts as a spindle poison and its reproductive toxicity as well as the induction of numerical chromosome aberrations and of micronuclei in somatic cells possibly may result from disturbance of microtubuli formation. Likewise, a causal relationship between aneuploidy and cancer has been repeatedly postulated. However, a critical survey of the data available on aneuploidogenic chemicals revealed insufficient evidence for such an association. Conceivably, other mechanisms may be responsible for the carcinogenic effects of the drug. The induction of thyroid tumors in rats by GF is apparently a consequence of the decrease of thyroxin levels and it is unlikely that such effects occur in GF-exposed humans. The appearance of hepatocellular carcinomas (HCC) in mice on GF-supplemented diet is preceded by various biochemical and morphological changes in the liver. Among these, hepatic porphyria is prominent, it may result from inhibition of ferrochelatase and (compensatory) induction of ALA synthetase. GF-induced accumulation of porphyrins in mouse liver is followed by cell damage and necrotic and inflammatory processes. Similar changes are known from certain human porphyrias which are also associated with an increased risk for HCC. However, the porphyrogenic effect of GF therapy in humans is moderate compared with that in the mouse model, although more detailed studies should be performed in order to clarify this relationship on a quantitative basis. A further important effect of GF-feeding in mice is the formation of Mallory bodies (MBs) in hepatocytes. These cytoskeletal abnormalities occur also in humans, although under different conditions; their appearance is associated with the induction of liver disease and HCC. Chronic liver damage associated with porphyria and MB formation, enhanced cell prolifera

Topics: Aneuploidy; Animals; Antifungal Agents; Carcinogenicity Tests; Cell Transformation, Neoplastic; Griseofulvin; Humans; In Vitro Techniques; Liver; Mice; Mutagenicity Tests; Neoplasms; Rats; Reproduction; Risk Assessment; Tissue Distribution

Lichen planus is a common oral dermatosis and it is one frequently encountered by oral surgeons. Lichen planus can be very difficult to treat, particularly when symptomatic in its erosive and ulcerated forms. This article describes several treatment modalities in the control of oral lichen planus including steroids, griseofulvin, vitamin A, cyclosporine, surgical excision, et al. Other features included consist of proper biopsy site selection, the need for annual re-examination, lichen planus's malignant potential, and when "not to treat."

Topics: Biopsy; Cell Transformation, Neoplastic; Cyclosporine; Griseofulvin; Humans; Lichen Planus, Oral; Steroids; Vitamin A

Mallory's body filament assembly includes polypeptides of the cytokeratin class of intermediate filaments and also higher molecular weight polypeptides normally found only in the cytokeratins of mature keratinocytes of the epidermis. These additional polypeptides may alter both the morphologic characteristics and increase the resistance to dissolution of the filaments by Ca++-activated protease activity. Thus, it is likely that the kinetics of Mallory's body filament assembly and dissolution favor growth of the filaments. In rodents fed certain carcinogens, Mallory's body formation has been accompanied by the induction of the oncofetoenzyme gamma-glutamyl transpeptidase (GGT), suggesting that Mallory's body formation, like GGT induction, is a phenotypic change related to the process of neoplastic transformation in rodents.

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cytoskeleton; gamma-Glutamyltransferase; Griseofulvin; Humans; Intermediate Filament Proteins; Keratins; Liver; Liver Diseases; Liver Neoplasms; Liver Neoplasms, Experimental; Lung; Lung Diseases; Phosphorylation; Protein Precursors

Topics: Animals; Antibodies; Carbamates; Cell Division; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Fluorescent Antibody Technique; Griseofulvin; Herbicides; Microtubules; Nitrous Oxide; Proteins; Tubulin

Topics: Aflatoxins; Animals; Benz(a)Anthracenes; Benzopyrenes; Carcinogens; Cell Transformation, Neoplastic; Cricetinae; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Environmental Exposure; Europe; Griseofulvin; Hydrocarbons; Japan; Male; Methylcholanthrene; Mice; Microsomes, Liver; Mitomycins; Neoplasms; Nitrosoguanidines; Plant Extracts; Prostate; Rats; United States

Mice were treated with griseofulvin (GF) containing diet or control diet for 12 months. The livers from mice fed griseofulvin showed large tumors that were excised and used for analysis. The infrared spectra from control liver tissue and tumor tissue from GF livers were measured and compared as a function of pressure up to 27 kbar. Many changes in the infrared spectral features of the tumor tissue were observed. Results showed that neoplasm formation involved structural modifications of nucleic acids, lipids, carbohydrates, and proteins in the liver cells, which were detected from the abnormal vibrations of the functional groups in these biomolecules. The amount of glycogen was dramatically decreased in the tumor tissue compared to the control tissue. Important changes in the strength of hydrogen-bondings in the phosphodiester backbone of the nucleic acids and in the C-O groups of tissue proteins and carbohydrates were observed. Stronger interchain interactions and thus close interchain packing among the lipids in the GF liver were evident. These results showed very close similarities with those obtained with other types of tumors such as human colon cancer, suggesting that a common pattern of molecular changes has been identified in neoplastic transformation.

Topics: Amides; Animals; Cell Transformation, Neoplastic; Glycogen; Griseofulvin; Hydrogen Bonding; Liver Neoplasms, Experimental; Mice; Mice, Inbred C3H; Phosphates; Pressure; Spectrophotometry, Infrared; Triglycerides

Three approaches have been taken to study simultaneously Syrian hamster cells and human cells in order to develop an extrapolation from the more established hamster system to human cells. On the Characterization of normal cells in comparison to tumor cells, human tumor cells and hamster tumor cells showed similarity in displaying anchorage independence, growth in suspension as micro tumor spheroids, and xenotumorigenicity in contrast to their respective normal cells; in addition, these tumor cells exhibited shorter population doubling time, higher saturation density, higher cloning efficiency, and higher fibrinolytic activity relative to their respective normal cell types. Other differences including ploidy change, contact inhibition on growth, serum requirement, and morphological transformation were also noted between human and hamster cells. On the application of microcarrier culture for a xenotumorigenicity test, the microcarrier technique seemed to have enhanced the sensitivity by reducing the number of inoculated tumor cells required for tumor formation. On the in vitro transformation of normal human and hamster cells, the highest efficiency of morphological transformation of hamster cells has been observed in the group treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by griseofulvin which was employed to enhance the transformation by disturbing the chromosome apparatus. However, no evidence of transformation was observed in the treated human cells thus far.

Topics: Animals; Cell Division; Cell Line; Cell Transformation, Neoplastic; Cricetinae; Embryo, Mammalian; Female; Fetus; Fibroblasts; Fibrosarcoma; Griseofulvin; Humans; Kinetics; Mesocricetus; Methylnitronitrosoguanidine; Pregnancy; Species Specificity; Tetradecanoylphorbol Acetate

Griseofulvin, 12-O-tetradecanoyl phorbol-13-acetate, melittin, epidermal growth factor, vinblastine, cytochalasin B, podophyllotoxin, colcemid, and colchicine were unable to transform cells but could increase from 8- to 40-fold the frequency of cell transformation by polyoma virus. The 3T3-like cells were resting at confluence and were exposed to the drug only during the 1st week after viral infection. Griseofulvin, a tumor promoter, reduced or increased the frequency of transformation depending on the dose with which the infected cells were treated. The antitumor activity of tumor promoters is discussed.

Topics: Cell Line; Cell Transformation, Neoplastic; Cell Transformation, Viral; Colchicine; Cytochalasin B; Epidermal Growth Factor; Griseofulvin; Melitten; Mutagens; Podophyllotoxin; Polyomavirus; Tetradecanoylphorbol Acetate; Vinblastine

Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Griseofulvin; Methylcholanthrene; Mice; Neoplasms; Neoplasms, Experimental