Carcinogens induce intrachromosomal recombination in human cells.
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.
Aubrecht
J
J
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Rugo
R
R
Schiestl
R H
RH
D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D004249:DNA Damage; D017353:Gene Deletion; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects*
D002273:Carcinogens; D007041:Hypoxanthine Phosphoribosyltransferase