Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemical responses detected in a sensitive new assay procedure.

Matthews, Edwin J.; Spalding, Judson W.; Tennant, Raymond W.

doi:10.1289/ehp.93101s2319

Cited by 30 publications

(13 citation statements)

References 17 publications

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“…In this context, and as alternative systems to the use of animals, in vitro cell cultures offer opportunities that are far from fully being exploited. In particular, the Balb/3T3 mouse fibroblast cell transformation system has been recognised as being relevant to testing the carcinogenic potential of chemicals, particularly those of an organic nature (6). A recent study on interlaboratory validation in the Balb/3T3 cell transformation assay proved the transferability of the protocol when two organic compounds were tested (a positive initiator and a tumour promoter; 19).…”

Section: Discussionmentioning

confidence: 99%

“…Three rodent-cell transformation assays, which involve cells with a finite life-span (Syrian hamster embryo [SHE]) cells) or immortalised cell lines (mouse fibroblasts Balb/3T3 and C3H/10T½), are most commonly used as predictive models for the carcinogenic potential of chemicals, including metal compounds (5). Although, the SHE and C3H/10T½ assays have been frequently used for this purpose (6)(7)(8)(9)(10)(11), the application of the Balb/3T3 assay to predict the carcinogenic potential of metals has been limited to As, Cd, Cr, Ni and V compounds, although a good concordance has been reported between in vitro transformation and in vivo carcinogenicity for organic compounds (6).…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Assessment of Cytotoxicity and Carcinogenic Potential of Chemicals: Evaluation of the Cytotoxicity Induced by 58 Metal Compounds in the Balb/3T3 Cell Line

et al. 2001

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A new, mechanistically based, in vitro strategy involving Balb/c 3T3 clone A31-1-1 mouse embryo fibroblasts has been proposed for the determination of the carcinogenic potential of inorganic chemicals, in order to establish priority of metal compounds to be tested and, whenever possible, to compare the in vitro results with the corresponding in vivo data. As a first step in this research, this study reports on the cytotoxic effects of 58 metal compounds in the Balb/3T3 cell line. After harmonisation and standardisation of the Balb/3T3 protocol, cells were exposed for 72 hours to a fixed dose (100μM) of 58 individual compounds. The cytotoxicity induced by some metal compounds was found to be related to their chemical form (for example, Cr(NO3)3 and Na2CrO4), suggesting that the Balb/3T3 cell line is a valuable cellular model in relation to this aspect of metal speciation. The results of the systematic study on the metal-induced cytotoxic effects in the Balb/3T3 cell line could be arbitrarily classified into three groups according to the degree of cytotoxicity. Group I includes 26 species that induced no observable effect or only a slight cytotoxic effect; Group II includes 13 metal compounds that exhibited an obvious degree of cytotoxicity; and Group III includes 19 metal species that displayed a strong cytotoxic response. Metal compounds of Groups II and III are considered to be of the highest priority for setting of dose–effect relationships for a subsequent in vitro study on metal-induced concurrent cytotoxicity and morphological transformation in the Balb/3T3 cell line.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Assessment of Cytotoxicity and Carcinogenic Potential of Chemicals: Evaluation of the Cytotoxicity Induced by 58 Metal Compounds in the Balb/3T3 Cell Line

et al. 2001

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“…In addition, these morphologicallytransformed cells closely resemble the in vivo neoplastic phenotype, and give rise to tumour formation when inoculated into immunosuppressed recipients (1,16,17). Many chemicals have been tested in various transformation assays, and their predictivity, specificity and sensitivity have been compared (12,(18)(19)(20)(21)(22)(23)(24).…”

Section: Cigarette Smoke-induced Morphological Transformation Of Bhasmentioning

confidence: 99%

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Weisensee

Poth²,

Roemer

et al. 2013

Altern Lab Anim

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In vitro cell transformation assays detect transformed cells that have acquired the distinct characteristics of malignant cells and thus model one stage of in vivo carcinogenesis. These assays have been proposed as surrogate models for predicting the non-genotoxic carcinogenic potential of chemicals. The Bhas 42 cell transformation assay, a short-term assay that uses v-Ha-ras-transfected Balb/c 3T3 cells, can detect the tumour promoter-like activities of chemicals, but has not previously been used with cigarette smoke. The particulate phase of cigarette smoke (total particulate matter [TPM]) is known to induce tumours in vivo in the mouse skin painting assay. Therefore, we investigated the ability of this Bhas cell assay to form morphologically transformed foci in vitro when repeatedly challenged with TPM from a standard research cigarette. TPM induced a dose-dependent increase in Type III foci, and a significant increase (up to 20-fold) in focus formation at moderately toxic concentrations between 5 and 60μg TPM/ml, with a peak at 20μg/ml. Three batches of TPM were tested in three independent experiments. Precision (repeatability and reproducibility) was calculated by using 0, 5, 10, and 20μg TPM/ml. Repeatability and reproducibility, expressed as the relative standard deviation obtained from the normalised slopes of the dose–response curves, were 17.2% and 19.6%, respectively; the slopes were 0.7402 ± 0.1247, 0.9347 ± 0.1316, and 0.8772 ± 0.1767 (increase factor*ml/mg TPM; mean ± SD); and the goodness of fit (r2) of the mean slopes, each derived from n = 6 repeats, was 0.9449, 0.8198, and 0.8344, respectively. This in vitro assay with Bhas 42 cells, which are regarded as already initiated in the two-stage paradigm of carcinogenesis (initiation and promotion), is able to detect cell transformation induced by cigarette smoke in a dose-dependent manner with a high sensitivity and good precision. Because this assay is fast and yields reliable results, it may be useful in product assessment, as well as for further investigation of the non-geno-toxic carcinogenic activity of tobacco smoke-related test substances.

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“…It is unknown if Ba ions are genotoxic to mammalian cells as they have not been investigated in these systems [Agency for Toxic Substances and Disease Registry, 1992; Dallas and Williams, 2001]. They induce morphological transformation of rodent cells [Matthews et al, 1993], but those data would only seem to confound the interpretation Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

Comparison of two particulate hexavalent chromium compounds: Barium chromate is more genotoxic than lead chromate in human lung cells

Wise

Schuler

Holmes

et al. 2004

Environ and Mol Mutagen

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Particulate hexavalent chromium [Cr(VI)] compounds are well-established human lung carcinogens. However, their carcinogenic mechanisms are poorly understood as most investigators have used soluble Cr(VI) compounds. Recent work from our laboratory has found that barium chromate (BC) is also cytotoxic and clastogenic. To understand how BC relates to existing data on other particulate Cr(VI) compounds, we compared its cytotoxicity and clastogenicity with lead chromate (LC), which has been used as a prototypical particulate Cr(VI) compound, in WTHBF-6 cells, a near-normal human lung cell line. We found that BC is a more potent cytotoxicant, inducing 67%, 12%, 3%, and 0% relative survival at concentrations of 0.1, 0.5, 1, and 5 microg/cm2, respectively, while LC induced 90%, 71%, 43%, and 15% survival at these same concentrations. We found that BC was also more clastogenic, damaging 22% and 49% of metaphase cells at 0.1 and 0.5 microg/cm2, and causing complete cell cycle arrest at 1 and 5 microg/cm2. By contrast, 0.1, 0.5, and 1.0 microg/cm2 LC damaged 10%, 27%, and 37% of metaphase cells, respectively, and complete cell cycle arrest was not observed until a concentration of 5 microg/cm2 was reached. We found that BC and LC both partially dissolved in complete medium in the presence of cells, producing similar extracellular concentrations. Both compounds were also comparable with respect to particle uptake and the amount of intracellular Cr ions. Considering previous reports showing that lead ions were inactive and that sodium chromate and LC have similar clastogenic potencies, these data suggest that BC genotoxicity may not be solely mediated by Cr ions, but also involve some clastogenic activity of barium ions.

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Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemical responses detected in a sensitive new assay procedure.

Cited by 30 publications

References 17 publications

In Vitro Assessment of Cytotoxicity and Carcinogenic Potential of Chemicals: Evaluation of the Cytotoxicity Induced by 58 Metal Compounds in the Balb/3T3 Cell Line

In Vitro Assessment of Cytotoxicity and Carcinogenic Potential of Chemicals: Evaluation of the Cytotoxicity Induced by 58 Metal Compounds in the Balb/3T3 Cell Line

Cigarette Smoke-induced Morphological Transformation of Bhas 42 Cells In Vitro

Comparison of two particulate hexavalent chromium compounds: Barium chromate is more genotoxic than lead chromate in human lung cells

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