Robert H. Heflich

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We previously reported that rat spleen T-cells and peripheral red blood cells that are deficient in glycosylphosphatidylinositol (GPI) synthesis [presumed mutants for the phosphatidylinositol glycan complementation group A gene (Pig-A)] could be detected by flow cytometry (FCM) as cells negative for GPI-linked markers (CD48 and CD59, respectively). To(More)
Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard. As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose-response data (Gollapudi et al., 2013), here we present analyses of 1-ethyl-1-nitrosourea (ENU) and(More)
In vivo genotoxicity tests play a pivotal role in genotoxicity testing batteries. They are used both to determine if potential genotoxicity observed in vitro is realised in vivo and to detect any genotoxic carcinogens that are poorly detected in vitro. It is recognised that individual in vivo genotoxicity tests have limited sensitivity but good specificity.(More)
7,12-Dimethylbenz[a]anthracene (DMBA) is a rodent carcinogen and a potent in vivo mutagen for the X-linked hypoxanthine guanine phosphoribosyl transferase (hprt) gene of rats and for the lacI transgene of Big Blue mice and rats. Although DMBA is also a powerful clastogen, molecular analysis of these DMBA-induced hprt and lacI mutations indicates that most(More)
Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA(More)
The gene coding for arylformamidase (Afmid, also known as kynurenine formamidase) was inactivated in mice through the removal of a shared bidirectional promoter region regulating expression of the Afmid and thymidine kinase (Tk) genes. Afmid/Tk -deficient mice are known to develop sclerosis of glomeruli and to have an abnormal immune system. Afmid-catalyzed(More)
Malachite green, a triphenylmethane dye used in aquaculture as an antifungal agent, is rapidly reduced in vivo to leucomalachite green. Previous studies in which female B6C3F1 mice were fed malachite green produced relatively high levels of liver DNA adducts after 28 days, but no significant induction of liver tumors was detected in a 2-year feeding study.(More)
The species specific response to 1,3-butadiene (BD), an important industrial chemical, was investigated by determining the influence of exposure duration and exposure concentration on the mutagenicity of BD in mice and rats and by defining the spectra of mutations in the Hprt gene T-cell mutants from control and BD-exposed mice. Female B6C3F1 mice and F344(More)
Male C57BL/6 neonates were treated on days 8 and 15 with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 6.5 or 26.2 mg/kg) or dimethylnitrosamine (DMN, 2.6 or 10.5 mg/kg). No tumors were seen in PhIP-treated animals at 15 months of age. Liver and lung tumor incidences in DMN-treated animals were 67-79 and 0-7%, respectively. In comparison with data(More)
Leucomalachite green is a persistent and prevalent metabolite of malachite green, a triphenylmethane dye that has been used widely as an antifungal agent in the fish industry. Concern over the use of malachite green is due to the potential for consumer exposure, evidence suggestive of tumor promotion in rodent liver, and suspicion of carcinogenicity based(More)