Critical periods of the mitotic cycle: Influence of aminopterin and thymidine on production of chromosomal aberrations by radiation in Crepis capillaris

Genetic effects of deoxyribonucleotide pool imbalances

“…Subsequent investigations have shown that thymine starvation induces not only single-and double-strand DNA breaks, but also degradation of prokaryotic DNA [Freifelder, 1969; Reiter and Ramareddy, 1969; Ramareddy and Reiter, 1970;Walker, 1970; Reichenbach et al, 1971; Breitman et al, 1972; Hill and Fangman, 1973;Yoshinaga, 1973; Buick and Harris, 1975;Bousque and Sicard, 1976; Perlman and Huberman, 19771. Similarly, chromosome breakage has been detected in plant, mammalian, and human cells following treatment with agents that induce thymidylate starvation [plants: Eigsti, 1942;Meyer, 1948; Kihlman, 1962; Taylor et al, 1962; Bell and Wolff, 1964;Sharma, 1971; Luchnik et al, 1976; Badr, 1982;mammalian cells: Dustin 1950a,b;Grampa and Dustin, 1952;Hsu et al, 1964a,b;Ockey et al, 1968; Murcia and Rombela, 1972;Hansmann, 1974;Maier and Schmid, 1976; Benedict et al, 1977; human cells: Bottura and Cotinho, 1965; Ryan et al, 1965;Jensen, 1967; Kaung and Swartzendruber, 1969; Voorhees et al, 1969; Melnyk et al, 1971; Jensen and Nyfors, 19811. Alkaline sucrose gradient centrifugation has been employed to demonstrate breakage and/or fragmentation of DNA strands during dTMP depletion of yeast Kunz and Haynes, 19821 and mammalian cells [Sedwick et al, 19811.…”

“…It has also been proposed that thymine nucleotides may act as signals to reduce the fidelity of the DNA replication complex by altering errorediting functions or the affinity for DNA precursors [Barclay and Little, 19811. However, it is important to note that the apparent mutagenicity of excess thymidine in cell culture and the potentiation of alkylation mutagenesis may be artifacts reflecting the differential sensitivities of mutant and nonmutant cells to elevated thymidine levels [Brennand and Fox, 1980;Brennand et al, 1981;Fox, 19821. Treatment with high concentrations of thymidine has also been found to induce a variety of chromosome and chromatid aberrations, including breaks and exchanges [Yang et al, 1966;Luchnik et al, 1976;Anderson et al, 19811. Simultaneous addition of deoxycytidine with thymidine reduced the extent of chromosome damage, indicating that the damage was related to unbalanced nucleotide pools.…”

Untitled

“…Similarly, ROS have been implicated in genotoxicity caused by particles and fibers. Genotoxicity of non-fibrous and fibrous particles is characterized by high production of ROS from inflammatory cells 75 . Flavonoids have been reported to possess a wide range of biochemical and pharmacological activities, both potentially detrimental and protective.…”

Hypothesis regarding a membrane-associated mechanism of biological action due to low-dose ionizing radiation

“…4). Many proposals have been made to explain why the action of low doses possesses specificity, among them the non-homogeneity of cell populations [30,34], the existence of two different repair systems for cytogenetic damage, an "adaptive" system in the range of LDE, and an emergency system triggered by further growth of DNA damage [35,36], etc. In this context, of interest might be the study on modification of dose-effect relationship in the dose range under consideration by the inhibitor of DNA damage repair caffeine and the radioprotector mercaptoethylamine (MEA) [31].…”