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Dive into the research topics where Gregory S. Probst is active.

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Featured researches published by Gregory S. Probst.


Mutation Research\/genetic Toxicology | 1987

A protocol and guide for the in vitro rat hepatocyte DNA-repair assay.

Byron E. Butterworth; John Ashby; Edilberto Bermudez; Daniel A. Casciano; Jon C. Mirsalis; Gregory S. Probst

The in vitro rat-hepatocyte DNA-repair assay is a valuable tool in assessing the genotoxic activity of chemical agents. An advantage of the assay is that the target cells themselves are metabolically competent, so that the patterns of metabolic activation and detoxification closely reflect those in the whole animal. This article provides a typical procedure and guidelines for conducting the rat in vitro hepatocyte DNA-repair assay.


Mutation Research | 1984

An evaluation of the L5178Y TK+/− mouse lymophoma forward mutation assay using 42 chemicals

T.J. Oberly; B.J. Bewsey; Gregory S. Probst

The L5178YTK+/- mouse lymphoma assay (MLA) has been utilized in several laboratories as a short-term test for chemical-induced forward mutation in cultured mammalian cells. In order to evaluate several technical modifications to the MLA, 42 chemicals representing 9 chemical classes were tested and the results were compared with those published elsewhere as well as with findings in a genetic toxicology test battery currently used in this laboratory. A positive response for the induction of TK-/- mutants was obtained for 26 chemicals. With the exception of p-aminophenol, all of these compounds were recognized mutagens or carcinogens and were representative of direct-acting and activation-dependent genotoxins. 16 compounds did not induce TK-/- mutants and among these were 5 compounds that were considered to be mutagens or carcinogens. A comparison of the results of this study with those published elsewhere revealed a strong agreement among findings for this test irrespective of minor technical variations. It was concluded that the MLA is a useful system for identifying chemical mutagens in mammalian cells and can serve as a valuable component in a genetic toxicology test battery.


Toxicological Sciences | 1992

Covalent protein modifications and gene expression changes in rodent liver following administration of methapyrilene: a study using two-dimensional electrophoresis.

N. L. Anderson; D. C. Copple; Raymond A. Bendele; Gregory S. Probst; Frank C. Richardson

The effect of methapyrilene (MP), a mitochondrial proliferator and presumed nongenotoxic carcinogen, has been examined in rodent liver by means of high-resolution two-dimensional electrophoretic analysis of total proteins. Using this approach, we have discovered protein modifications in rat liver resulting from 1 week MP treatment that suggest the involvement of a reactive drug metabolite. The restriction of these molecular charge modifications to mitochondrial proteins indicates that such a reactive metabolite must be generated and confined within the mitochondrion. Quantitative changes in numerous nonmitochondrial proteins are also observed. Following a 4-week recovery period, almost all the 1-week treatment changes are reversed, reestablishing a protein pattern close to that of the controls. At the end of a 10-week exposure, the mitochondrial protein modifications are increased and are accompanied by a variety of quantitative protein changes indicative of a large shift in gene expression and/or cell type composition. When a 4-week untreated recovery period follows the 10-week treatment, small quantitative changes persist. In the mouse, where MP appears not to induce mitochondrial proliferation or tumorigenesis, 1 week treatment nevertheless produces mitochondrial protein changes in vivo consistent with attack by a reactive metabolite, but at a level substantially lower than that seen in the rat. Features of the mitochondrial protein modification indicate that it is covalent, does not involve cysteine or tryptophan, and results from binding of a negatively charged adduct. The possibility that the putative reactive metabolite could also attack mitochondrial (but not nuclear) DNA suggests that MP could be genotoxic in an unconventional way. Detection of protein modification by two-dimensional gel analysis appears to offer a general method for the detection and characterization of processes generating reactive metabolites.


Cancer Letters | 1980

The induction of unscheduled DNA synthesis by antihistamines in primary hepatocyte cultures

Gregory S. Probst; Steven B. Neal

The autoradiographic identification of chemically-induced, unscheduled DNA synthesis in primary cultures of adult rat hepatocytes is currently being validated as a predictive test for mutagens/carcinogens. Of 8 antihistaminic drugs tested, 2, pyrilamine maleate and tripelennamine HCl, were positive for unscheduled DNA synthesis. Further investigation of the mutagenic/carcinogenic potential of these compounds in alternate test systems is suggested.


Food and Chemical Toxicology | 1985

Evaluation of ochratoxin A for mutagenicity in a battery of bacterial and mammalian cell assays

A.M. Bendele; Steven B. Neal; T.J. Oberly; C.Z. Thompson; B.J. Bewsey; Leo E. Hill; Marcia A. Rexroat; William W. Carlton; Gregory S. Probst

Ochratoxin A (OA), a nephrotoxic mycotoxin, was evaluated for genotoxic potential in a battery of in vitro and in vivo assays. OA was not mutagenic to Salmonella typhimurium, either with or without metabolic activation, in the plate incorporation (Ames) test at concentrations of 50-600 micrograms OA/plate or in the gradient plate assay at concentrations of 0.1-1000 micrograms OA/ml. No induction of unscheduled DNA synthesis was evident in primary cultures of rat hepatocytes exposed to concentrations of OA ranging from 0.000025 to 500 micrograms/ml. In the mouse lymphoma forward mutation assay, exposure of L5178Y TK+/- mouse lymphoma cells to OA did not increase the numbers of L5178Y TK-/- mutants. There was no significant difference between the numbers of sister-chromatid exchanges in cells from OA-treated Chinese hamsters and those in cells from the negative-control animals.


Mutation Research\/genetic Toxicology | 1991

Genotoxicity studies on the preemergence herbicide trifluralin

Michael L. Garriott; Elizabeth R. Adams; Gregory S. Probst; John L. Emmerson; T.J. Oberly; Delinda E.F. Kindig; Steven B. Neal; B.J. Bewsey; Marcia A. Rexroat

This paper reports the results of studies conducted within the Lily Research Laboratories and discusses additional studies with trifluralin that have been reported in the literature


Journal of Toxicology and Environmental Health | 1980

Comparison of three in vitro assays for carcinogen‐induced DNA damage

Gregory S. Probst; Leo E. Hill; B.J. Bewsey

DNA damage induced by five ultimate carcinogens and five procarcinogens was evaluated by three methods: (1) DNA strand breaks in Crandall feline kidney (CRFK) cells measured by alkaline sucrose gradient centrifugation; (2) unscheduled DNA synthesis (UDS) in CRFK, Syrian hamster embryo (SHE), and rat hepatocyte cultures measured by liquid scintillation counting; and (3) UDS in CRFK, SHE, and rat hepatocyte cultures measured by autoradiography. DNA strand breaks were observed with three procarcinogens and four ultimate carcinogens. Only two procarcinogens and two ultimate carcinogens could be identified by liquid scintillation counting. A positive autoradiographic response for UDS was observed in CRFK cells with four of five ultimate carcinogens and one procarcinogen. SHE cells showed a positive autoradiographic response for UDS with all ultimate carcinogens and three procarcinogens. The autoradiographic system with primary rat hepatocyte cultures was the only one in which a positive response for DNA damage was elicited for all 10 carcinogens.


Mutation Research\/genetic Toxicology | 1988

The in vivo effect of 2,6-xylidine on induction of micronuclei in mouse bone marrow cells.

Joseph W. Parton; Gregory S. Probst; Michael L. Garriott

The ability of 2,6-xylidine to produce chromosome breakage and/or spindle malformation in vivo was evaluated by an assessment of the capacity of the compound to induce micronuclei in bone marrow polychromatic erythrocytes. Male ICR mice were administered a single oral dose of 350, 175 or 87.5 mg/kg of 2,6-xylidine by oral gavage and bone marrow was extracted from the femurs 24, 48 and 72 h thereafter. The frequency of micronuclei in animals treated with 2,6-xylidine was not different from that observed for the corresponding solvent treated controls.


Cell Biology and Toxicology | 1987

Influence of age, sex and strain on the in vitro induction of unscheduled DNA synthesis in rat hepatocyte primary cultures.

Gregory S. Probst; Leo E. Hill

The activity of chemical-induced unscheduled DNA synthesis was evaluated in hepatocyte primary cultures from Fischer 344 and Sprague-Dawley rats over a period of two years. In this two-year study hepatocytes from both sexes and strains were prepared from animals 2, 8, 14, 20 and 25 months of age and UDS was measured by autoradiography following treatment with N-methyl-AP-vitro-N-nitrosoguanidine and 2-acetylaminofluorine. A dose-related positive response occurred for both compounds throughout the study in hepatocytes from male and female Fischer rats and male Sprague-Dawley rats. The magnitude of the response was greatest in hepatocytes from male Fischer rats and a markedly lower response in unscheduled DNA synthesis occurred in all cultures prepared from animals of both strains and sexes at 20 and 25 months of age. Hepatocytes from female Sprague-Dawley rats showed a low level of unscheduled DNA synthesis with N-methylN′-vitro-N-nitrosoguanidine throughout the study. The most striking finding was the absence of a UDS response to 2-acetylaminofuorene by hepatocytes from Sprague-Dawley females at the 8, 14, 20 or 25 month periods. The results indicate an age-related decrease in chemical-induced unscheduled DNA synthesis activity among rats.


Mutation Research | 1986

Thymidine kinase activity and trifluorothymidine resistance of spontaneous and mutagen-induced L5178Y cells in RPMI 1640 medium

T.J. Oberly; B.J. Bewsey; Gregory S. Probst

L5178Y/TK+/- cells were treated with 3-methylcholanthrene (3MC) in order to obtain thymidine-kinase-deficient mutants (TK-/-) which were resistant to trifluorothymidine (TFTr). Clones of TK-/- cells were harvested from soft agar and adapted to growth in suspension culture. The phenotype of the TK-/- and TK+/- clones was confirmed by measuring thymidine kinase activity. These studies were undertaken with cells from 16 3MC-induced large colony clones (lambda TK-/-), 21 3MC-induced small colony clones (sigma TK-/-), and 51 spontaneous sigma TK-/- clones. Thymidine kinase activity was absent in all of the lambda TK-/- and sigma TK-/- 3MC-induced clones and also in 49 of 51 sigma TK-/- spontaneous clones. After at least 50 generations in suspension culture, TFTr was retained by 80% of the 3MC-induced lambda TK-/- cells, by 75% of the 3MC-induced sigma TK-/- cells, and by 89% of the spontaneous sigma TK-/- cells. The collective results showed that 86 of the 88 TFTr colonies examined lacked thymidine kinase activity and indicate that at least 98% of all TFTr colonies seen in the L5178Y assay are true TK-/- mutants.

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Daniel A. Casciano

University of Arkansas at Little Rock

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