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Hprt mutant frequency and molecular analysis of Hprt mutations in rats treated with mutagenic carcinogens
Authors:Casciano D A  Aidoo A  Chen T  Mittelstaedt R A  Manjanatha M G  Heflich R H
Institution:

a National Center for Toxicological Research, Division of Genetic and Reproductive Toxicology, Jefferson, AR 72079, USA

b Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

c Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

d Environmental Carcinogenesis Division, NHEERL/USEPA, Research Triangle Park, NC 27711, USA

Abstract:Much of the progress in the field of cancer research has come from the increased understanding of the molecular events associated with the initiation and accumulation of mutational events associated with carcinogenesis. Genetic toxicologists have developed a number of in vitro and in vivo non-mammalian and mammalian systems to predict those genetic events required to induce the cancer process. Several model rodent systems have been proposed that have the ability to detect and quantify in vivo somatic mutation in endogenous genes and transgenes and relate the nature of the mutation to the specific type of chemical damage. One such system, the rat lymphocyte hypoxanthine guanine phosphoribosyl transferase (Hprt) assay is described in this review. Data are presented that describe mutant induction and mutational spectra in N-ethyl-N-nitrosourea (ENU), 7,12-dimethylbenzoa]anthracene (DMBA) and thiotepa (TEPA) treated rats.
Keywords:Hprt  Rat lymphocyte assay  DNA sequencing  Mutation frequency  Mutational spectra  Thiotepa  N-ethyl-N-nitrosourea  7  12-dimethylbenzp[a]anthracene
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