Carcinogens induce intrachromosomal recombination in human cells. 1995

J Aubrecht, and R Rugo, and R H Schiestl
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.

A major portion of new cases of cancer may be linked to environmental carcinogens. The Ames (Salmonella) test is currently the most widely used short-term test to predict carcinogenic properties of compounds. However, approximately 50% of all carcinogens have been sufficiently tested in long-term animal bioassays do not induce mutations in the Salmonella assay, and many of these carcinogens are also not detectable by other short-term assays. In the work described here we determined the effect of carcinogen exposure on intrachromosomal recombination in a human cell line. The recombination events caused the deletion of one copy of a duplication of exons 2 and 3 of the hprt gene. We found that these deletion events were induced by exposure to the Salmonella assay positive carcinogens UV, gamma-rays and methyl methanesulfonate, as well as the Salmonella assay negative carcinogens Aroclor 1221, benzene and thiourea. These data may further support the accumulating evidence that recombination and deletions may be important in carcinogenesis.

UI MeSH Term Description Entries
D007041 Hypoxanthine Phosphoribosyltransferase An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8. Guanine Phosphoribosyltransferase,HPRT,Hypoxanthine-Guanine Phosphoribosyltransferase,IMP Pyrophosphorylase,HGPRT,HPRTase,Hypoxanthine Guanine Phosphoribosyltransferase,Phosphoribosyltransferase, Guanine,Phosphoribosyltransferase, Hypoxanthine,Phosphoribosyltransferase, Hypoxanthine-Guanine,Pyrophosphorylase, IMP
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions

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