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British Medical Journal Jun 1955
Topics: Hodgkin Disease; Leukemia; Lymphoma; Triazines; Triethylenemelamine
PubMed: 14363905
DOI: No ID Found -
Cancer Letters Nov 1983The dorsal skin of female CD-1 mice was treated with triethylenemelamine (TEM) to determine whether this agent acted either as a complete carcinogen or as an initiator...
The dorsal skin of female CD-1 mice was treated with triethylenemelamine (TEM) to determine whether this agent acted either as a complete carcinogen or as an initiator of carcinogenesis. A dose of 0.01-1.0 mumol of TEM applied once a week for 32 weeks to the skin of the backs of mice did not produce any detectable tumors. A dose of 2.5 mumol applied once a week over the same period produced only a single papilloma in a group of 20 mice. However, when mice were treated with a single dose of 1 mumol of TEM followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week, 88% of the mice produced papillomas after 28 weeks. Using the same protocol, a single application of hexamethylmelamine (HMM), pentamethylmelamine (PMM), or melamine followed by promotion with TPA had no significant tumor initiating activity. These data suggest that TEM acts primarily as an initiator of two-stage carcinogenesis.
Topics: Animals; Carcinogens; Cocarcinogenesis; Female; Mice; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors; Triethylenemelamine
PubMed: 6640512
DOI: 10.1016/0304-3835(83)90080-0 -
Environmental and Molecular Mutagenesis 1989Keratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known...
Keratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known chromosome-damaging agent triethylenemelamine (TEM). The chemical was applied to the skin of HRA/Skh hairless mice at concentrations corresponding to those reported to initiate cancer in initiation-promotion assays. A significant dose-related depression in keratinocyte cell recovery occurred over the dose range 0.3-1 mg TEM/mouse (single or multiple treatments). Under the same conditions, a dose-related induction of micronuclei was observed using the cytokinesis-block method with cytochalasin B. A similar frequency of micronuclei was detected in binucleate cells from mice treated with single or multiple applications of TEM. Mice held for 12-48 h post-treatment, before removal of skin for in vitro culture, yielded highest micronuclei frequencies. These results indicate that the same target cell population, skin keratinocytes, can be used to investigate both genotoxicity and carcinogenesis, and that micronucleus induction in these cells may be a sensitive signal of skin cancer initiation.
Topics: Animals; Cells, Cultured; Cytochalasin B; Male; Mice; Mice, Hairless; Micronucleus Tests; Skin; Skin Neoplasms; Triethylenemelamine
PubMed: 2753023
DOI: 10.1002/em.2850140102 -
Mutation Research Mar 1995The mutagenicity of the trifunctional alkylating (or cross-linking) agent TEM (triethylenemelamine or 2,4,6-tris(1-aziridinyl)-1,3,5-triazine) in the adenine-3 (ad-3)... (Comparative Study)
Comparative Study
The mutagenicity of the trifunctional alkylating (or cross-linking) agent TEM (triethylenemelamine or 2,4,6-tris(1-aziridinyl)-1,3,5-triazine) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this chemical to determine the spectrum of specific-locus mutations induced in a lower eukaryotic organism and to compare this spectrum with that induced in the mouse. Specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. These loci control two sequential biochemical reactions in the purine biosynthetic pathway. A 0.1 M solution of TEM was used to treat conidial suspensions of H-12 for 20, 40, 80, 120, or 170 min to obtain dose-response curves for (1) inactivation of conidia, and (2) the induction of specific-locus mutations in the ad-3 region. These experiments demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the TEM-induced ad-3 mutations from each of the five treatment groups to distinguish between the different genotypic classes and subclasses. The overall data base from these genetic studies demonstrates that TEM-induced ad-3 mutations result predominantly (95.5% [769/805]) from gene/point mutations at the ad-3A and ad-3B loci, and from a low percentage (4.5% [36/805) of multilocus deletion mutations. In addition, TEM induces an unusually high frequency of multiple-locus mutations with sites of recessive lethal damage closely linked with the ad-3 region. Comparison of the dose-response curves for the major classes and subclasses of TEM-induced ad-3 mutations demonstrates (1) that gene/point mutations and multilocus deletion mutations increase as the 1.4 power of TEM treatment time, and (2) that the two classes of TEM-induced multiple-locus ad-3 mutations consisting of gene/point mutations with separate sites of recessive lethal damage increase at about the 1.96 power of TEM treatment time. When the data from the present specific-locus studies are compared with those in the mouse, we find, insofar as such comparisons are possible, that a similar spectrum of specific-locus mutations has been induced by TEM in each assay system.
Topics: Animals; DNA Damage; DNA, Fungal; Dose-Response Relationship, Drug; Genes, Fungal; Genes, Lethal; Genes, Recessive; Genetic Complementation Test; Mice; Mutagenesis; Neurospora crassa; Point Mutation; Triethylenemelamine
PubMed: 7870102
DOI: 10.1016/0027-5107(94)00174-4 -
Modern Problems in Ophthalmology 1977Newer concepts in the diagnosis and treatment of retinoblastoma are briefly discussed. The role of ultrasonography, EMI scanning and LDH assays in the anterior chamber...
Newer concepts in the diagnosis and treatment of retinoblastoma are briefly discussed. The role of ultrasonography, EMI scanning and LDH assays in the anterior chamber are evaluated. The greatest problems in differential diagnosis in recent years have been larval granulomatosis caused by Toxicara canis, Coat's disease and unclassifiable retinal dysplasias. The Ellsworth-Reese classification is discussed. The "cure rate" has been widely misinterpreted as survival and has led to many misapprehensions in the treatment of unilateral disease. The cases in group IV now do better for a variety of reasons and the results in orbital cases have been more extensively studied. The genetics of retinoblastoma have been intensively studied in our laboratory along with Dr. Kitchin and some newer concepts are briefly discussed. The relative roles of orthovoltage, external beam 60Co, linear accelerators and betatron are presented. Dosage level is distinctly related to radiation complications, especially retinal vascular necrosis and fatal radiation-induced neoplasms. The relationship of the latter to the pattern of inheritance is to be stressed. Chemotherapy has been used both as an adjuvant to radiation and for the destruction of micrometastases and a new protocol is described. The results of treatment are presented to update the 1966 report at the Gonin Club Meeting in Munich.
Topics: Aqueous Humor; Cyclophosphamide; Eye Neoplasms; Humans; Isoenzymes; L-Lactate Dehydrogenase; Mutation; Neoplasm Metastasis; Retinoblastoma; Triethylenemelamine; Ultrasonography; Vincristine
PubMed: 876116
DOI: No ID Found -
A.M.A. Archives of Ophthalmology Apr 1954
Topics: Humans; Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Radiation; Radiotherapy; Retina; Retinal Neoplasms; Retinoblastoma; Triethylenemelamine
PubMed: 14360881
DOI: 10.1001/archopht.1955.00930010507007 -
Nature Dec 1957
Topics: Animals; Chromosomes; Mice; Translocation, Genetic; Triethylenemelamine
PubMed: 13493527
DOI: 10.1038/1801364a0 -
Giornale Italiano Di Chemioterapia 1954
Topics: Hodgkin Disease; Humans; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms; Triethylenemelamine
PubMed: 13191624
DOI: No ID Found -
Mutation Research Apr 1975To determine the feasibility of the micronuclei procedure for cytogenetic studies, a comparatively weak chromosome breaking agent, trimethylphosphate (TMP) and the...
To determine the feasibility of the micronuclei procedure for cytogenetic studies, a comparatively weak chromosome breaking agent, trimethylphosphate (TMP) and the potent alkylating agent, triethylenemelamine (TEM) were evaluated. The procedure followed was that of Matter and Schmid with the following modifications: (a) direct flushing of bone marrow with 0.2 ml calf fetal serum. (b) air drying slides for a period of only I h, and (c) the use of pH 6.0 phosphate buffer to dilute both Wright and Giemsa stains. With this technique a dose response curve was generated for both TMP and TEM, using mice as the experimental animal. With TMP, a doubling over background was found when a concentration of 0.5 g/kg per day for five days was administered. To establish a statistically significant doubling dose over the control, a minimum of five animals must be used with 2000 polychromatic cells being analyzed per animal. Of the two antischistosomal agents tested, hycanthone yielded an increase of 20-fold in the number of micronuclei over control at 40 mg/kg administered i.p. for five days, while with niridazole no increase in micronuclei at several concentrations tested both by single and multiple injection was found. The results obtained with these compounds compare favorably with what has been reported for the standard in vivo metaphase analysis.
Topics: Alkylating Agents; Animals; Bone Marrow; Bone Marrow Cells; Cell Nucleus; Dose-Response Relationship, Drug; Erythrocytes; Evaluation Studies as Topic; Genetic Techniques; Hycanthone; Mice; Niridazole; Phosphates; Thioxanthenes; Time Factors; Triethylenemelamine
PubMed: 1095914
DOI: 10.1016/0027-5107(75)90319-x -
British Journal of Cancer Sep 1958
Topics: Hodgkin Disease; Mechlorethamine; Nitrogen Mustard Compounds; Triethylenemelamine
PubMed: 13596499
DOI: 10.1038/bjc.1958.54