In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

Kowalski, L. A.; Laitinen, A. M.; Mortazavi‐Asl, B.; Wee, R. K.‐H.; Erb, H. E.; Assi, K. P.; Madden, Z.

doi:10.1002/1098-2280(2000)35:4<300::aid-em4>3.3.co;2-q

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…On the other hand, as a stably transfected cloned cell population, Bhas 42 cells does not require de novo transfection every time and can be maintained as a stable cell source sensitive to chemical transformation. Kowalski and colleagues [77,78] also established an oncogenic gene-carrying clone (T1: bovine papilloma virus type I DNA transfected C3H10T1/2 cells) and predicted carcinogenicity or non-carcinogenicity of 92% [77] and 77% [78] of chemicals with repeated assays by co-culturing T1 and C3H10T1/2 cells. Therefore, for transformation assay purposes, using cloned cell populations transfected with an oncogenic gene, such as Bhas 42 and T1 Downloaded by [University of Colorado -Health Science Library] at 21: 40 30 March 2015 cells, may be more desirable since such target cells appear to be more stable and to provide higher degree of reproducibility.…”

Section: Transformation-sensitive Cell Linessupporting

confidence: 90%

Transformation Assay in Bhas 42 Cells: A Model Using Initiated Cells to Study Mechanisms of Carcinogenesis and Predict Carcinogenic Potential of Chemicals

Sasaki

Umeda

Sakai

et al. 2015

Journal of Environmental Science and Health, Part C

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Transformation assays using cultured cells have been applied to the study of carcinogenesis. Although various cell systems exist, few cell types such as BALB/c 3T3 subclones and Syrian hamster embryo cells have been used to study chemically induced two-stage carcinogenesis. Bhas 42 cells were established as a clone by the transfection with the v-Ha-ras gene into mouse BALB/c 3T3 A31-1-1 cells and their subsequent selection based on their sensitivity to 12-O-tetradecanoylphorbol-13-acetate. Using Bhas 42 cells, transformed foci were induced by the treatment with nongenotoxic carcinogens, most of which act as tumor promoters. Therefore, Bhas 42 cells were considered to be a model of initiated cells. Subsequently, not only nongenotoxic carcinogens but also genotoxic carcinogens, most of which act as tumor initiators, were found to induce transformed foci by the modification of the protocol. Furthermore, transformation of Bhas 42 cells was induced by the transfection with genes of oncogenic potential. We interpret this high sensitivity of Bhas 42 cells to various types of carcinogenic stimuli to be related to the multistage model of carcinogenesis, as the transfection of v-Ha-ras gene further advances the parental BALB/c 3T3 A31-1-1 cells toward higher transforming potential. Thus, we propose that Bhas 42 cells are a novel and sensitive cell line for the analysis of carcinogenesis and can be used for the detection of not only carcinogenic substances but also gene alterations related to oncogenesis. This review will address characteristics of Bhas 42 cells, the transformation assay protocol, validation studies, and the various chemicals tested in this assay.

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Section: Transformation-sensitive Cell Linessupporting

confidence: 90%

Transformation Assay in Bhas 42 Cells: A Model Using Initiated Cells to Study Mechanisms of Carcinogenesis and Predict Carcinogenic Potential of Chemicals

Sasaki

Umeda

Sakai

et al. 2015

Journal of Environmental Science and Health, Part C

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“…Since the number of N-nitroso compounds is rather low (n = 4) and the degree of association is mainly determined by one data point (NNK), more N-nitroso compounds need to be tested in a cell transformation assay (CTA) in the presence of metabolic activation in order to pass a definitive judgment. Kowalski et al (2000) evaluated an in vitro transformation test for predicting the rodent carcinogenicity TD 50 (taken from the CPDB) against a testing database of 64 chemicals including both genotoxic and non-genotoxic carcinogens and carcinogens that normally require addition of a S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T½-mouse embryo fibroblast cell line (T1).…”

Section: In Vitro Transformation Assays Dunkel Et Al (1981) Comparedsupporting

confidence: 76%

Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Buist

DeVito

Goldbohm

et al. 2015

Regulatory Toxicology and Pharmacology

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“…An in vitro test was used by Kowalski et al (2000) in order to predict rodent carcinogenicity of chemicals. The assay uses focus formation in a stable, bovine papilloma virus type 1 (BPV-1) DNA carrying C3H/10T1⁄2 mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction.…”

Section: Cell Transformation Assaymentioning

confidence: 99%

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

2010

EFS2

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The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion on the use of polyvinylpyrrolidone-vinyl acetate (PVP/VA) copolymer in food supplements. PVP/VA copolymer is poorly absorbed orally and largely excreted intact in the faeces. No genotoxicity data are available. Both a 28-day and a 90-day feeding study with PVP/VA copolymer in the rat, revealed a NOAEL of 1000 mg/kg bw/day (highest dose tested). Oral administration of PVP/VA copolymer to male/female rats for 24 months and to male/female dogs for 52 weeks revealed NOAELs of 2800 mg/kg bw/day and 2500 mg/kg bw/day respectively (highest doses tested). No reproductive or developmental toxicity data are available. The exposure to PVP/VA copolymer from its use in food supplements and in pharmaceuticals is 23.4 mg/kg bw/day (adult high consumers) and 16 mg/kg bw/day (child high consumers). The toxicological database was too limited to derive an ADI. From the given range of NOAELs and the intake of PVP/VA copolymer, a Margin of Safety (MOS) varying from 43 to 120 for adults and from 63 to 175 for children can be calculated. These MOS are considered sufficient given the lack of absorption of PVP/VA, the fact that the NOAELs were the highest doses tested and that exposure estimates are based on worst case assumptions. From the maximum residual levels of VA, Margins of Exposure (MOE) of > 10 6 were calculated. The MOE for hydrazine were above 10000. The Panel concluded that the residual levels of hydrazine (up to a maximum of 1.0 mg/kg in the final product) are unlikely to be of safety concern, but considered it would be prudent to lower the level of hydrazine as far as reasonably achievable. The Panel concluded that the use of PVP/VA copolymer in solid food supplements as a binding/coating agent is unlikely to be of safety concern at the proposed uses. © European Food Safety Authority, 2010 KEY WORDSPolyvinylpyrrolidone-vinyl acetate copolymer, CAS Registry Number 25086-89-9, vinyl acetate; polyvinylpyrrolidone; copolyvidon; copovidone; 1-vinyl-2-pyrrolidone-vinyl acetate copolymer; 2-pyrrolidinone, 1-ethenyl-, polymer with ethenyl acetate. SUMMARYFollowing a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on polyvinylpyrrolidone-vinyl acetate (PVP/VA) copolymer when used as a food additive.The present opinion deals with the safety of PVP/VA copolymer for use in food supplements in tablet form as a binding/coating agent in an amount of up to 10% of weight per tablet, for a tablet weight of 1000 mg.PVP/VA copolymer is a copolymer produced by polymerisation of the monomers N-vinyl-2-pyrrolidone (NVP) and vinyl acetate (VA). The substance will be used in food supplement tablets as a binding agent and as a coating agent.No absorption, distribution, metabolism and excretion (ADME) studies were provided by the petitioner. It is reported in literature that PVP/VA copolymer, given its high weight average molecular weight of about ...

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In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

Cited by 3 publications

References 7 publications

Transformation Assay in Bhas 42 Cells: A Model Using Initiated Cells to Study Mechanisms of Carcinogenesis and Predict Carcinogenic Potential of Chemicals

Transformation Assay in Bhas 42 Cells: A Model Using Initiated Cells to Study Mechanisms of Carcinogenesis and Predict Carcinogenic Potential of Chemicals

Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS: Alternative approaches

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

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