Acetic acid, a potent agent of tumor progression in the multistage mouse skin model for chemical carcinogenesis

Rotstein, Joel; Slaga, Thomas J.

doi:10.1016/0304-3835(88)90243-1

Cited by 20 publications

(9 citation statements)

References 5 publications

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“…This inducement, coupled with the removal of the promoting agent, should then result in some foci that continue to grow in the absence of a promoting agent (i.e., that are promoter independent). The work of Rotstein and Slaga ( 12) has further suggested that progression in the mouse skin model is not affected by withdrawal of the promoting agent; by analogy, promoter-independent foci in the liver model may represent focal hepatic lesions in the stage of progression. Since the number of promoter-independent foci is a quantitative indication of progression, it can be used to rank by potency putative progressor agents and processes.…”

Section: Discussionmentioning

confidence: 99%

“…Additional evidence of the need for a minimum of two genetic changes to evoke malignant neoplasia comes from studies on transformation resulting from cotransfection studies with two activated oncogenes (24). The initiation-promotion-progression (IPP) protocol of chemical carcinogenesis was suggested by Potter (9) and has been used to demonstrate the ability of complete carcinogens ( 10, 1 1, 14), selectively cytotoxic agents ( 12), and free radical generators (1 3) to induce progression in the mouse skin model. The IPP protocol also models these three stages in the rat liver (1 8, 19, 25, 26) and, coupled with the technique of quantitative stereology, permits the investigation of each stage separately (19,25,26).…”

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confidence: 99%

“…A similar conclusion was reached later by Hennings et al (10, 1 1) using the IPP model in which direct-acting mutagens were used as the putative progressor agents. Although classes of chemical agents that present a carcinogenic risk primarily through progressor action have not been established, complete carcinogens, cytotoxic agents, and clastogenic agents are active during this stage of mouse epidermal carcinogenesis (10)(11)(12)(13)(14). In addition, urethane has been shown to result in an increased incidence of malignant neoplasms and thus can be considered to be a progressor agent for the skin (29), further suggesting that agents other than direct-acting mutagens are able to begin the progression process.…”

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confidence: 99%

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The Initiation-Promotion-Progression Model of Rat Hepatocarcinogenesis

Dragan¹,

Sargent²,

Xu³

et al. 1993

Experimental Biology and Medicine

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Carcinogenesis is a multistage process consisting of the three distinct stages: initiation, promotion, and progression. The initiation-promotion-progression (IPP) protocol models these stages and establishes a method whereby agents that possess a carcinogenic risk can be classified as acting primarily at any one or combination of these stages. In one hepatocarcinogenesis IPP protocol, rats were initiated with 10 mg of diethylnitrosamine/kg body wt at 5 days of age, started on the promoting agent phenobarbital at weaning, subjected to a 70% partial hepatectomy at 6 months, and, at the peak of proliferation, given a putative progressor agent, ethylnitrosourea ([ENU] 100 mg/kg, ip) or hydroxy-urea ([HU] 3 x 150 mg/kg, ip). Administration of the promoting agent was discontinued after the progressor agent was given, and the rats were sacrificed 6 months later. The number and volume fraction of promoter-independent (growth in the absence of the promoting agent) altered hepatic foci (AHF) were then determined by quantitative stereology. The number of such AHF increased with either ENU or HU treatment compared with animals not given a progressor agent. In addition, hepatocytes isolated from animals subjected to an IPP regimen with ENU as the progressor agent exhibited a greater degree of chromosomal breakage and aneuploidy than animals not given a second initiator. A variation of this model, in which the promoting agent was maintained after administration of the progressor agent, was examined. In this IPP model, the number of heterogeneous AHF (foci-in-foci) increased after application of the progressor agent (ENU or HU). An increased incidence of hepatocellular carcinoma was also observed in animals subjected to the IPP protocol when promotion was maintained until sacrifice. Thus, the characteristics of progression--increased chromosomal damage, aneuploidy, growth of AHF in the absence of continued tumor promotion, the presence of foci-in-foci, and an increased incidence of malignant neoplasia--have been used as end points for the demonstration of progressor activity by ENU. In addition, the potential progressor activity of HU and benzene has been demonstrated with the IPP model of rat hepatocarcinogenesis.

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Section: Discussionmentioning

confidence: 99%

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The Initiation-Promotion-Progression Model of Rat Hepatocarcinogenesis

Dragan¹,

Sargent²,

Xu³

et al. 1993

Experimental Biology and Medicine

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“…While the toxicity profile of haloacetic acids is incomplete, trichloroacetic acid is known to be teratogenic [28]. Acetic acid is a very weak tumor promoter in the multistage mouse skin model for chemical carcinogenesis but is a potent agent in the tumor progression phase of the model [29]. A solution of 7% acetic acid, as typically used in SYPRO Red and SYPRO Orange stains, is comparable to vinegar and thus should not be considered hazardous.…”

Section: Discussionmentioning

confidence: 99%

Fluorescence detection of proteins in sodium dodecyl sulfate-polyacrylamide gels using environmentally benign, nonfixative, saline solution

Steinberg¹,

Lauber

Berggren³

et al. 2000

Electrophoresis

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“…Studies in our laboratory examining acetic acid as a tumor-progressing agent also support selective toxicity as a potential mechanism in tumor progression. Treatment of papilloma-bearing mice biweekly with acetic acid (667 pmol) led to a 2-fold increase in both the percentage of animals with carcinomas and the cumulative number of carcinomas formed (22). The dosage used here may well have had toxic effects.…”

Section: Agents and Mechanisms That Increase Tumor Progressionmentioning

confidence: 91%