Cell transformation by chemical agents — A review and analysis of the literature

Heidelberger, Charles; Freeman, Aaron E.; Pienta, Roman J.; Sivak, Andrew; Bertram, John S.; Casto, Bruce C.; Dunkel, Virginia C.; Francis, Mary W.; Kakunaga, Takeo; Little, John B.; Schechtman, Leonard M.

doi:10.1016/0165-1110(83)90036-2

Cited by 207 publications

(33 citation statements)

References 97 publications

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“…In contrast to MCA, all four chemicals induced dose-related increases in both cytotoxic and transformation responses over a relatively short range of treatment doses. Previously, BaP and MNNG have also been demonstrated to be active in this assay (1)(2)(3)(4). BaP was selected as the positive control for the BALB/c-3T3 transformation assay over the other three chemicals, because many carcinogens in rodent bioassay are thought to require cellular metabolism to become carcinogenic and are not considered direct-acting mutagenic chemicals (7,8).…”

Section: Introductionmentioning

confidence: 96%

“…There have been a number of reports describing chemical-induced morphological transformation of BALB/c-3T3 cells (1)(2)(3)(4), and these investigations invariably used 3-methylcholanthrene (MCA) as the positive control. In addition, government agencies (5) and scientific committees (6) MCA induced very high transformation responses over a two log range in concentrations from 0.1 to 10 pLg/ml, whereas most test chemicals, such as N-methyl-Nnitro-N'-nitrosoguanidine (MNNG), induced transformation over a limited range of treatment doses (i.e., 0.5-2.0 p,g/mL MNNG; data not presented).…”

Section: Introductionmentioning

confidence: 99%

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Transformation of BALB/c-3T3 Cells: II. Investigation of Experimental Parameters That Influence Detection of Benzo[a]pyrene-Induced Transformation

Matthews¹

1993

Environmental Health Perspectives

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Benzo[alpyrene (BaP) induced significant morphological transformation of clone A31-1-13 BALB/c-3T3 cells without exogenous activation. Therefore, BaP was selected as a model to determine the internal consistency of detection of chemical-induced transformation. BaP induced a continuum of type I-III foci of different sizes, and the ratio of type I-III to type III foci/vessel was usually about 2-fold. The major finding was that BaP induced highly significant transformation responses, and the magnitude of these responses were inversely correlated with the cytotoxicity of the treatment doses. Thus, the induction of BaP-induced transformation behaved as though it was caused by a mutational event. Variability among responses were shown to depend on the serum lot and the cryopreserved ampule of cells. In addition, experiments with low spontaneous transformation responses had an impaired ability to detect BaP; however, experiments with high or normal spontaneous responses had a normal ability to detect BaP. Because the expression of BaP-induced transformation depended on both the cytotoxicity of the treatment and the cumulative number of mitoses, the frequency of BaP-induced transformation should be reported as the number of foci/vessel, but not expressed as the number of foci/viable cell surviving the chemical treatment. These conclusions are important because the same 110 experiments described in this report were also used to evaluate the transformation responses of many different carcinogenic and noncarcinogenic chemicals. These data are being reported separately.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Transformation of BALB/c-3T3 Cells: II. Investigation of Experimental Parameters That Influence Detection of Benzo[a]pyrene-Induced Transformation

Matthews¹

1993

Environmental Health Perspectives

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“…Thus on a small scale, the free radical-induced liberation of iron from an iron-binding protein may reflect an evolved signaling pathway; on a larger scale, however, it may result in the wholesale destruction of the organism. Iron compounds have been reported to be mutagenic in mammalian culture cells, as detected by Syrian hamster embryo cell transformation/ viral enhancement assay (Heidelberger et al, 1983), base tautomerization in rat hepatocyte cultures (Abalea et al, 1999) and genetic alterations in the mouse lymphoma tetraacetic acid (EDTA), disodium (054448), Triton-X-100 (2020130), Tris base (2044122), and 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid (HEPES, 75277) were purchased from SRL, India. Sodium chloride , sodium hydroxide (Merck-1310-73-2), sodium bicarbonate , and low melting point (LMP) agarose (Bangalore Genei FC37) were purchased from Merck, Germany and Bangalore Genei, India.…”

Section: Introductionmentioning

confidence: 99%

Iron induced genotoxicity: attenuation by vitamin C and its optimization

Parveen

Ahmad

Shadab

2014

Interdisciplinary Toxicology

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Vitamin C (VC) is a well-known antioxidant and strong free radical scavenger. Its antioxidant activity is useful for protection of cellular macromolecules, particularly DNA, from oxidative damage induced by different agents. This study was undertaken to evaluate the optimum level of VC in attenuating the chromosome aberrations (CAs) and DNA damage after iron sulfate (FeSO 4 ) acute administration in Wistar rats. The results exhibited that the increase of CAs and DNA damage induced by FeSO 4 , 200 mg Fe/kg, could be reduced significantly by VC pretreatment at the dose of 500 mg/kg (p<0.001), but not in the 100 mg/kg group. The findings provide evidence that VC at the dose of 500 mg/kg exerted a possible protective effect against FeSO 4 induced CAs and DNA damage. The possible mechanisms of VC may be attributed to its property as a free radical scavenger or to its indirect action in reducing the level of reactive oxygen species (ROS).

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“…Similarly, many laboratories have not reported spontaneous transformed colonies of Syrian hamster embryo (SHE) cells in the SHE colony transformation assay (6,7); however, other laboratories report background activities for this assay (8). In contrast, spontaneous transformation has been routinely detected in both the BALB/c-3T3 (9)(10)(11)(12)(13) and Simian adenovirus 7/SHE (SHE/SA7) transformation assays (14)(15)(16). The mechanism of spontaneous transformation in the SHE/SA7 system has been correlated with the insertion ofviral DNA into the genome of the host cells (15).…”

Section: Introductionmentioning

confidence: 99%

Transformation of BALB/c-3T3 Cells: I. Investigation of Experimental Parameters That Influence Detection of Spontaneous Transformation

Matthews¹

1993

Environmental Health Perspectives

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The frequency of spontaneous morphological transformation is an important variable in measuring chemical-induced transformation in BALB/c-3T3 clone A-31-1-13 cell cultures. Data from 110 experiments, which included benzo[a]pyrene control groups and other chemical treatment groups, were analyzed for factors that influenced spontaneous transformation. Spontaneous transformants demonstrated a continuum of morphological variants (type I, II, and III foci) that fit a normal distribution if converted to log1o. The magnitude of transformation depended on the ampule of cryopreserved cells and the serum lot. Although the average frequency was approximately 0.71 x 10' (type III foci/cell that survived and proliferated to confluence), the absolute number of foci/vessel increased in proportion to the surface area of the culture vessel. Thus, the frequency of spontaneous transformation was directly related to the cumulative number of mitoses that occurred in forming the contact-inhibited monolayer. These data are consistent with a hypothesis that spontaneous transformation in BALB/c-3T3 cells is a mutational event or some other single-step phenomenon.

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Cell transformation by chemical agents — A review and analysis of the literature

Cited by 207 publications

References 97 publications

Transformation of BALB/c-3T3 Cells: II. Investigation of Experimental Parameters That Influence Detection of Benzo[a]pyrene-Induced Transformation

Transformation of BALB/c-3T3 Cells: II. Investigation of Experimental Parameters That Influence Detection of Benzo[a]pyrene-Induced Transformation

Iron induced genotoxicity: attenuation by vitamin C and its optimization

Transformation of BALB/c-3T3 Cells: I. Investigation of Experimental Parameters That Influence Detection of Spontaneous Transformation

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