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J T Arnold

Publications and source records attributed to J T Arnold.

5 recordsLinked to original sources
PubMed1990

Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents.

Twenty-eight compounds were screened for chemopreventive activity by using a rat tracheal epithelial cell transformation inhibition assay. In this new assay, chemicals were tested for their ability to inhibit the formation of transformed rat tracheal epithelial cell colonies which arise following exposure to the carcinogen benzo(a)pyrene. The 15 positive compounds were N-acetylcysteine, bismuththiol, calcium glucarate, (+/-) catechin, diallyl disulfide, glycaric acid, D-glucaro-1,4-lactone, N-(4-hydroxyphenyl)retinamide, D-limonene, mesna, retinoic acid, rutin, quercetin, silymarin, and taurine. In examining the nature of compounds that inhibited rat tracheal epithelial cell transformation, several possible chemopreventive mechanisms appeared to be predominant: compounds that were positive (a) increased glutathione levels or enhanced conjugation; (b) increased cytochrome P-450 activity; (c) displayed nucleophilic activity; or (d) induced differentiation. Thirteen compounds were negative in the rat tracheal epithelial transformation inhibition assay: crocetin, difluoromethylornithine, ellagic acid, esculetin, enoxalone, ibuprofen, levamisole, nordihydroguaiaretic acid, L-2-oxothiazolidine-4-carboxylate, piroxicam, sodium butyrate, D-alpha-tocopherol acetate, and polyethylene glycol 400. It was evident from these results that this assay would not detect compounds that were (a) anti-promoting in nature; (b) glutathione inhibitors; (c) differentiation inhibitors; (d) O6-methylguanine inhibitors; (e) organ specific; or (f) inactive. The rat tracheal epithelial cell transformation inhibition assay appeared to identify chemopreventive compounds that act at early stages of the carcinogenic process.

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PubMed1989

Evaluation of a rat tracheal epithelial cell culture assay system to identify respiratory carcinogens.

To evaluate a short-term epithelial cell assay system to detect respiratory carcinogens, primary cultures of rat tracheal epithelial cells were exposed to a series of 17 compounds and scored for morphologically transformed cell colonies 28 days later. The test compounds included known carcinogens and noncarcinogens in volatile or liquids form. Tracheal epithelial cells were isolated from F344 rats, plated onto collagen-coated dishes, and exposed to the test compounds on day 1 for 24 hours. At day 30 the cultures were fixed, stained, and scored for colonies having a density greater than 1,300 cells/min2. With standardized protocols, such colonies are very infrequent in media and solvent control cultures. Concentration levels for each chemical were chosen over a range from nontoxic to toxic levels. Highly positive compounds in this assay included benzo(a)pyrene, benzo(l)acean-thyrlene, 3-methylcholanthrene, and formaldehyde. Compounds which were negative in this assay included pyrene, benzo(e)pyrene, and 4-nitroquinoline-N-oxide. Examining the concordance of in vitro results with whole animal carcinogenesis studies revealed an accuracy of 88% with one false-positive and one false-negative compound. The results of these studies indicate that the rat tracheal epithelial cell assay may be useful in identifying potential respiratory carcinogens in our environment.

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PubMed1988

In vivo and in vitro characteristics of early carcinogen-induced premalignant phenotypes in cultured rat tracheal epithelial cells.

The initial stages of neoplastic transformation in respiratory tract epithelial cells were defined and studied by characterizing a series of morphologically transformed cell colonies from carcinogen-exposed rat tracheal epithelial (RTE) cell cultures both in vivo and in vitro. RTE cells were isolated from Fischer 344 rats, plated on collagen-coated dishes, and exposed to 7,12-dimethylbenz[a]anthracene on day 1 for 24 h. Between days 26 and 30, single colonies of morphologically altered cells were isolated and classified into three major classes based on cell density. Following replating, the cells were tested for their ability to grow on various substrates and in various culture media. Generally, Class II and III cells exhibited a higher colony forming efficiency when replated on various substrates. Class III cells appeared to grow better than Class I or II cells in complete medium, while Class I cells grew better in medium without 3T3 conditioning factors. At early passage levels, the population doubling times were longer for Class I cells than for Class II cells. Class III cells had the shortest population doubling times. The various cell lines were also placed into denuded tracheal grafts. Untreated cells produced a normal mucociliary epithelium, while Class I cells produced a simple cuboidal epithelium. Class II and III cells formed a highly atypical and usually malignant epithelia. Inoculation of the three classes of cells into nude mice provided confirming evidence of the benign nature of Class I cell lines and the malignant nature of some Class II cell lines and all of the Class III cell lines.

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PubMed1987

Colony formation enhancement of rat tracheal and nasal epithelial cells by polyacetate, indole alkaloid, and phorbol ester tumor promoters.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), teleocidin and two polyacetate tumor promoters (aplysiatoxin and debromoaplysiatoxin) have been tested for their effect on colony forming efficiency (CFE) of rat tracheal and nasal turbinate epithelial cells. In rat tracheal epithelial (RTE) cells, all four compounds stimulated colony formation by up to 8-fold using picomolar concentrations of aplysiatoxin and teleocidin, whereas TPA and debromoaplysiatoxin were effective in the nanomolar range. In addition, teleocidin and the other promoters increased the number of cells in colonies by 3- to 5-fold resulting in larger colonies, most notably above concentrations that maximally stimulated CFE. In contrast, rat nasal epithelial cells were only marginally stimulated by these tumor promoters to form colonies. The results indicate that there is regional specificity in responses to tumor promoters and RTE cells can act as very sensitive biological indicators of the presence of these three classes of tumor promoters with diverse structure.

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