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Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses. Cell harvest times could also be extended(More)
Chromosome aberrations can occur by secondary mechanism(s) associated with cytotoxicity, induced by chemicals that do not attack DNA. Aberrations are formed from DNA double-strand breaks, and DSBs are known to be induced by nonmutagenic (Ames test negative) noncarcinogens at toxic levels [Storer et al. (1996): Mutat Res 368:59-101]. Here, 8 of 12 of these(More)
Vorinostat (SAHA, Zolinza), a histone deacetylase inhibitor, is assessed in nonclinical studies to support its approval for cutaneous T-cell lymphoma. Vorinostat is weakly mutagenic in the Ames assay; is clastogenic in rodent (ie, CHO) cells but not in normal human lymphocytes; and is weakly positive in an in vivo mouse micronucleus assay. No effects are(More)
International guidelines for cytotoxicity limits for the in vitro chromosomal aberration assay require reductions in cell growth of greater than 50%. This sets no upper limit on toxicity and there is concern about the number of false or irrelevant results obtained in the aberration assay, i.e., positive results at toxic dose levels only, with no evidence(More)
3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp) were evaluated in vitro for their potential to induce DNA adducts, DNA strand breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and mutations. All compounds produced DNA adducts in calf thymus DNA in the presence of rat liver S9. In cultured rat hepatocytes, all(More)
O6-Methylguanine (O6MeG) is important in induction of chromosome aberrations (abs), with the unusual property that new abs are produced in the second cycle after treatment; cells lacking repair by O6-alkylguanine DNA-alkyltransferase (AGT) have more abs at the second division (M2) than at the first (M1). These second-cycle abs are likely caused by attempted(More)
Good cell culture practice and characterization of the cell lines used are of critical importance in in vitro genotoxicity testing. The objective of this initiative was to make continuously available stocks of the characterized isolates of the most frequently used mammalian cell lines in genotoxicity testing anywhere in the world ('IVGT' cell lines). This(More)
Rat sperm motility and membrane integrity were compared as endpoints for viability. Sperm motility was measured by computer-assisted semen analysis (CASA), whereas membrane integrity was assessed by flow cytometric analysis of sperm stained with two nucleic acid stains, SYBR-14 and propidium iodide. The two techniques were compared in experiments that(More)
Video-assisted parathyroidectomy (VAP) is a new approach to parathyroid exploration for primary hyperparathyroidism (PH). We examined the VAP learning curve and hypothesized that compared with conventional minimally invasive parathyroidectomy (MIS), VAP has similar complication rates and the added benefit of a shorter hospital length of stay. Using a(More)