Genotoxic effects of paracetamol in V79 Chinese hamster cells. 1988

J K Hongslo, and T Christensen, and G Brunborg, and C Bjørnstad, and J A Holme
Department of Toxicology, National Institute of Public Health, Oslo, Norway.

Paracetamol was studied for possible genotoxic effects in V79 Chinese hamster cells. Paracetamol (0.5 mM for 30 min) reduced the rate of DNA synthesis in exponentially growing V79 cells to about 50% of control. A further decrease in the DNA synthesis was seen during the first 30 min after termination of paracetamol exposure. Paracetamol (3 and 10 mM for 2 h) caused a small increase in DNA single-strand breaks, as measured by the alkaline elution technique. After 16 h elution, the amount of DNA retained on the filters was 79 and 70% of controls in cells treated with 3 and 10 mM paracetamol respectively. No indication of DNA damage was seen in measuring the effect of paracetamol (0.25-10 mM for 2 h) on unscheduled DNA synthesis in growth-arrested cultures of V79 cells. At the highest concentrations (3 and 10 mM paracetamol), decreased unscheduled DNA synthesis was observed. Also UV-induced DNA-repair synthesis was inhibited by 3 and 10 mM paracetamol. DNA-repair synthesis was, however, inhibited at a much higher concentration than that inhibiting replicative DNA synthesis. The number of sister-chromatid exchanges (SCE) increased in a dose-dependent manner on 2 h exposure to paracetamol from 1 mM to 10 mM. At the highest dose tested (10 mM), the number of SCE increased to 3 times the control value. Co-culturing the V79 cells with freshly isolated mouse hepatocytes had no further effect on the paracetamol induced sister-chromatid exchanges. The present study indicates that paracetamol may cause DNA damage in V79 cells without any external metabolic activation system added.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
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
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response

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