Unscheduled Synthesis

The concept of unscheduled synthesis and the autoradiographic experiment that measures it were introduced by Rasmussen and Painter (1964). Their publication presented the first evidence for DNA repair in mammalian cells. Cells are grown on slides or coverslips, irradiated or 

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Perocco P, Pane G, Bolognesi S, et al. 1982. Increase of sister chromatid exchange and unscheduled synthesis of deoxyribonucleic acid by acrylonitrile in human lymphocytes in vitro. Scand J Work Environ Health 8 290-293. 

NDPA has exhibited genotoxicity in bacteria Salmonella typhimurium, Escherichia colt) and mammalian cells (mouse lymphoma, Chinese hamster) and caused DNA effects (fragmentation, unscheduled synthesis, repair) in rat hepatocytes and chromosome aberrations in Chinese hamster cells. ... 

Many of the end points for tests described in this chapter, including gene mutation, chromosome damage, and oncogenicity, develop as a consequence of damage to or chemical modification of DNA. Most of these tests, however, also involve metabolic events that occur both prior to and subsequent to the modification of DNA. Some tests, however, use events at the DNA level as end points. One of these, the unscheduled synthesis of DNA in mammalian cells, is described in some detail the others are summarized briefly. 

Cleaver JE, Thomas GH (1981) Measurement of unscheduled synthesis by autoradiography. In Friedberg EC, Hanawalt PC (eds) DNA Repair. A laboratory Manual of Research Procedures. Marcel Dekker, New York, pp 277-287... 

Gledhill BL, Darzynkiewicz Z (1973) Unscheduled synthesis of DNA during mammalian spermatogenesis in response to UV irradiation. J Exp Zool 183 375-382... 

Durrant LG, Margison GP, Boyle JM (1981) Effects of 5-methylnicotinamide on mouse LI210 exposed to N-methyl-N -nitrosourea mutation induction, formation and removal of methyla-tion products in DNA and unscheduled synthesis. Carcinogenesis 2 1013-1017... 

Assay for mitotic recombination in yeast and Drosophila Assay for unscheduled DNA synthesis in cultured hepatocytes and rodents... 

Human lung fibroblasts Unscheduled DNA synthesis - Waters et al. 1982... 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

Rat hepatocyte culture Unscheduled DNA synthesis No data - Hoechst 1984c... 

Hoechst. 1984d. Evaluation of Hoe 002671 - substance technical - in the rat primary hepatocyte unscheduled DNA synthesis assay Final report. Conducted for Hoechst Aktiengesellschaft, Frankfurt, Germany. Litton Bionetics, Inc., Kensington, MA. FBI project no. 10400-001.[unpublished study]... 

Rat (hepatocyte unscheduled DNA synthesis) breaks) DNA damage (unspecified) Mirsalis et al. 1989... 

Rat primary hepatocytes (unscheduled DNA synthesis) DNA damage No data — Shimadaetal. 1985... 

Mirsalis JC, Tyson CK, Steinmetz KL, et al. 1989. Measurement of unscheduled DNA synthesis and S-phase synthesis in rodent hepatocytes following in vivo treatment Testing of 24 compounds. Environ Mol Mutagen 14 155-164. 

In vitro unscheduled DNA synthesis (UDS) in mammalian cells test OECD... 

Glauert HP, Kennan WS, Sattler GL, et al. 1985. Assays to measure the induction of unscheduled DNA synthesis in cultured hepatocytes. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 371-373. 

Hurtt ME, Bentley KS, Working PK. 1987. Effects of acrylamide and acrylonitrile on unscheduled DNA synthesis (UDS) in rat spermatocytes. Environ Mutagen 9 49-50. 

Mammalian cells Human (lymphocytes) Unscheduled DNA synthesis Perocco et al. 1983... 

DNA effects Damage to DNA (Deoxyribonucleic acid) by a chemical or material may result in genotoxic effects such as mutations, which in turn may lead to carcinogenicity. Damage to DNA causes the cell to manufacture new DNA to compensate for the loss or damage. This can be assessed by evaluating the formation of newly synthesized DNA. Unscheduled DNA Synthesis... 

Assays for DNA Effects DNA damage and repair unscheduled DNA synthesis in vitro / ... 

Williams, G.M. (1976a). Carcinogen-induced DNA repair in primary rat liver cell cultures a possible screen for chemical carcinogens. Cancer Lett. (Shannon, Ire.) 1 231-236. Williams, G.M. (1976b). The detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 37 1845-1851. 

Probst GS, McMahon RE, Hill LE, et al. 1981. Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte cultures A comparison with bacterial mutagenicity using 218 compounds. Environ Mutagen 3 11-32. 

Rat, mouse, and/or hamster hepatocytes Unscheduled DNA synthesi s NA - Maslansky and Williams 1981 Probest et al. 1981... 

Chlordecone (1.67-10.00 mg/L) increased the frequency of sister chromatid exchange in CHO cells but only in the absence of S9 activation and only in the presence of cell-cycle delay the results were confirmed in a repeat trial (Galloway et al. 1987). By contrast, chlordecone alcohol was negative for sister chromatid exchange induction both with and without S9 activation (Galloway et al. 1987). Subcytotoxic doses of mirex did not induce unscheduled DNA synthesis in primary hepatocytes recovered from rats, mice, or hamsters (Maslansky and Williams 1981 Williams 1980). Similar results were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 1,000 pmol/L mirex. Chlordecone was also uniformly negative in unscheduled DNA synthesis assays of primary rat hepatocytes (Probst et al. 1981 Williams 1980). 

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