Chromosome aberrations induced in vitro: mechanisms, delayed expression, and intriguing questions.
Chromosome aberrations, including breakage and rearrangement and numerical changes, are important in carcinogenesis, heritable mutations, embryonic loss, and developmental abnormalities. We can detect DNA reactive agents in in-vitro chromosome aberrations assays, but aberrations are also induced by chemical that do not directly interact with DNA. This article discusses briefly some important aspects of using aberrations in genetic toxicology testing but concentrates on highlights of recent research on aberrations, in particular two areas: (1) persistence through multiple cell cycles of changes that lead to chromosome aberrations, and (2) the relations among DNA synthesis inhibition, DNA damage, cell cycle regulation, and genomic instability, expressed as chromosome breakage, gene amplification, and aneuploidy. An understanding of these mechanisms not only may lead to insights into carcinogenesis but ultimately may help us to interpret results of chromosome aberration tests and to develop a rational assessment of the degree of human risk implied by a positive aberration test.
Galloway
S M
SM
Merck Research Laboratories, West Point, Pennsylvania 19486.
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D003582:Cytogenetics / Q000379:methods*; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D005821:Genetic Techniques; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity
D009153:Mutagens; D004247:DNA