ascorbic-acid and Rhabdomyosarcoma

The ability of ascorbic acid and a number of its derivatives to suppress replication of Herpes simplex virus type I was investigated in human rhabdomyosarcoma cell line. In parallel, interaction of the test compounds with carbon- and oxygen-centered radicals formed on radiolysis of hydroxyl-containing organic compounds was studied using the steady state radiolysis method. It has been shown that 2-O-glycoside of ascorbic acid, displaying marked antiviral properties against Herpes simplex virus type I, is also capable of inhibiting fragmentation and recombination reactions of α-hydroxyl-containing carbon-centered radicals while not affecting processes involving oxygen-centered radicals.

Topics: Antiviral Agents; Ascorbic Acid; Carbon; Cell Line, Tumor; Free Radical Scavengers; Herpesvirus 1, Human; Humans; Oxygen; Radiation, Ionizing; Reactive Oxygen Species; Rhabdomyosarcoma

Genomic DNA was isolated from subcutaneous masses observed in CD-1 and p53+/- heterozygous mice during the course of carcinogenicity studies in the vehicle control groups. These masses resulted after daily subcutaneous injection of an antioxidant vehicle with a pH adjusted to 3-4. The vehicle was 1.0% ascorbic acid plus 0.05% sodium metabisulfite in 0.75% saline in a dosing volume of 10 ml/kg/day. These masses were first palpable after 13 and 37 weeks of dosing among p53+/- and CD-1 mice, respectively. By week 26, the incidence of these masses was 89% and 80% in male and female p53+/- mice, respectively (n = 15 mice/sex) and was 0% in both male and female CD-1 mice (n = 60 mice/sex). These masses originated from panniculus carnosus muscle. Histopathological examination of the p53+/- mouse masses indicated the tumors to be sarcomas of spindle-cell origin. The histopathological examination of the masses in the CD-1 mice revealed fibrosarcomas. Five mice/sex/strain were randomly selected from a pool of mice that developed these masses in the course of the two studies. Frozen tissues from these masses were used to examine the DNA for loss of the functional p53 allele in the p53+/- mice (i.e., loss of heterozygosity, or LOH) or for loss of one of the alleles in the wild type (p53+/+) CD-1 mice by the polymerase chain reaction (PCR) technique. Loss of the functional allele was observed only in the tumor from one p53+/- male mouse. These results support a nongenotoxic mechanism for these injection site masses.

Topics: Alleles; Animals; Antioxidants; Ascorbic Acid; Carcinogenicity Tests; Female; Fibrosarcoma; Heterozygote; Injections, Subcutaneous; Loss of Heterozygosity; Male; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Rhabdomyosarcoma; Sensitivity and Specificity; Soft Tissue Neoplasms; Sulfites; Tumor Suppressor Protein p53

Monoclonal antibodies reactive with the tissue form of type VI collagen were used to isolate the type VI collagen polypeptides from cultured fibroblasts and muscle cells. Two [35S]methionine-labeled polypeptides of 260 and 140 kD were found intracellularly, in the medium, and in the extracellular matrix of metabolically labeled cells. These polypeptides were disulfide cross-linked into very large complexes. The 260- and 140-kD polypeptides were intimately associated and could not be separated from each other by reduction without denaturation. In the absence of ascorbic acid, both polypeptides accumulated inside the cell, and their amounts in the medium and in the matrix were decreased. These results suggest that both the 260- and the 140-kD polypeptides are integral parts of the type VI collagen molecule. Examination of type VI collagen isolated from the intracellular pool by electron microscopy after rotary shadowing revealed structures corresponding to different stages of assembly of type VI collagen. Based on these images, a sequence for the intracellular assembly of type VI collagen could be discerned. Type VI collagen monomers are approximately 125 nm long and are composed of two globules separated by a thin strand. The monomers assemble into dimers and tetramers by lateral association. Only tetramers were present in culture media, whereas both tetramers and multimers were found in extracellular matrix extracts. The multimers appeared to have assembled from tetramers by end-to-end association into filaments that had prominent knobs and a periodicity of approximately 110 nm. These results show that, unlike other collagens, type VI collagen is assembled into tetramers before it is secreted from the cells, and they also suggest an extracellular aggregation mechanism that appears to be unique to this collagen.

Topics: Animals; Antibodies, Monoclonal; Ascorbic Acid; Cells, Cultured; Collagen; Extracellular Matrix; Fibroblasts; Humans; Leiomyosarcoma; Muscles; Osteosarcoma; Protein Processing, Post-Translational; Rats; Rhabdomyosarcoma

Topics: Animals; Ascorbic Acid; Benzo(a)pyrene; Benzopyrenes; Carcinogens; Female; Fibrosarcoma; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Rhabdomyosarcoma; Sarcoma, Experimental

The s.c. infection of 10 mg benzo(a)pyrene dissolved in 1 ml tricaprylin induced in Wistar rats local malignant tumors, such as fibrosarcoma, rhabdomyosarcoma, and polymorph cell sarcoma. The growth of the tumors was relatively rapid, reaching weights of 140-155 g before rats died 142-168 days after the administration of the carcinogen. On the contrary, under the same experimental conditions, high doses of Vitamin C about 525 mg/day/rat administered orally in drinking water (total amount of Vitamin C 55 g/rat corresponding to 40% of their body weight ) inhibited to a great extent the benzo(a)pyrene carcinogenesis. Only one slowly growing rhabdomyosarcoma (13 g of weight) was developed showing characteristic damage of malignant cells and partial replacement of the neoplastic area with granuloma tissue. The significance ov Vitamin C for cancer prevention and treatment is discussed.

Topics: Animals; Ascorbic Acid; Benzopyrenes; Dose-Response Relationship, Drug; Fibrosarcoma; Neoplasms, Experimental; Rats; Rhabdomyosarcoma; Sarcoma, Experimental