Inhibition of morphological transformation induced with N-methyl-N'-nitro-N-nitrosoguanidine in cultures of hamster embryo cells by 5'-bromo-2'-deoxyuridine-photolysis. 1978

S G Mironescu

The present study was performed in order to determine whether type III transformed foci induced by N-methyl-N'-nitro-N-nitrosoguanidine originate from the small subpopulation of cells stimulated by the carcinogen to enter DNA synthesis. During the last 30 min of variable treatment periods using different doses of N-methyl-N'-nitro-N-nitrosoguanidine, administered alone or in association with the thymidine analogue, 5'-bromo-2'-deoxyuridine (0.98 x 10(-5)M), the density-inhibited monolayers of hamster embryo cells were exposed to fluorescent light and then assayed for abnormal growth patterns by the focus formation method. Mock-irradiated cultures as well as monolayers whose medium lacked N-methyl-N'-nitro-N-nitro-soguanidine, 5'-bromo-2'-deoxyuridine, or both, served as controls. The cytotoxicity of 5'-bromo-2'- deoxyuridine + N-methyl-N'-nitro-N-nitrosoguanidine + photolysis (BMP) protocol on confluent as well as logarithmically growing hamster embryo cells was estimated in single-cell survival experiments. Plating efficiency determinations have demonstrated that, unlike their actively growing counterparts, confluent hamster embryo cell monolayers are extremely resistant to the cytotoxic effects of the BMP protocol. The quantitative transformation assays indicated that: (1) in non-illuminated cultures addition of 5'-bromo-2'-deoxyuridine to carcinogen-containing medium does affect transformation frequency of hamster embryo cells in the sense that the incidence of type III foci did not subside at later intervals during the post-carcinogen administration period as it did in the absence of the analogue; (2) irradiation of N-methyl-N'-nitro-N-nitrosoguanidine and halogenated pyrimidine analogue-treated cultures with fluorescent light practically suppressed transformation; (3) analogue-added and analogue-removed experiments pointed out that the event(s) on which 5'-bromo-2'-deoxyuridine fluorescent light sensitization of morphological transformation largely depends, takes place between 5 and 15 h after N-methyl-N'-nitro-N-nitrosoguanidine administration, i.e., during the period of maximal carcinogen-stimulated DNA synthesis; and (4) neither fluorescent light nor 5'-bromo-2'-deoxyuridine, singly or in combination, were able to transform cultures of hamster embryo cells. These findings are strong indirect arguments for the concept that carcinogen-induced DNA synthesis and the initiation of transformed clones are causally related.

UI MeSH Term Description Entries
D008769 Methylnitronitrosoguanidine A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties. Methylnitrosonitroguanidine,Nitrosomethylnitroguanidine,Nitrosonitromethylguanidine,MNNG,N-Methyl-N'-nitro-N-nitrosoguanidine,N Methyl N' nitro N nitrosoguanidine
D010782 Photolysis Chemical bond cleavage reactions resulting from absorption of radiant energy. Photodegradation
D001973 Bromodeoxyuridine A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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