Prevalidation study of the Syrian hamster embryo (SHE) cell transformation assay at pH 7.0 for assessment of carcinogenic potential of chemicals

Maire, Marie-Aline; Pant, Kamala; Poth, Albrecht; Schwind, Karl-Rainer; Rast, C.; Bruce, Shannon; Sly, Jamie; Kunz-Bohnenberger, Susanne; Kunkelmann, Thorsten; Engelhardt, G.; Schulz, Markus; Vasseur, Paule

doi:10.1016/j.mrgentox.2011.12.007

Cited by 14 publications

(11 citation statements)

References 24 publications

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“…The merits of incorporating the SHE CTA into test batteries for safety and toxicological testing have long been debated. Although recent efforts by ECVAM to pre-validate the assay in terms of reproducibility [13] , [21] , [32] and by the OECD to provide standardised assay guidelines, are well advanced [33] , a lack of molecular understanding forging a mechanistic link between the assay’s end point and carcinogenesis has hindered its widespread adoption as a suitable animal alternative [3] . Here, we have further evaluated the SHE CTA by picking representative examples of MT and non-transformed colonies prior to staining in Giemsa and characterising molecular events leading to unlimited growth potential in cells derived from benzo(a)pyrene-induced morphologically transformed (MT) clones.…”

Section: Discussionmentioning

confidence: 99%

A mechanistic evaluation of the Syrian hamster embryo cell transformation assay (pH 6.7) and molecular events leading to senescence bypass in SHE cells

Pickles

Pant

Mcginty

et al. 2016

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Section: Discussionmentioning

confidence: 99%

A mechanistic evaluation of the Syrian hamster embryo cell transformation assay (pH 6.7) and molecular events leading to senescence bypass in SHE cells

Pickles

Pant

Mcginty

et al. 2016

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…Two important factors have largely been ignored in the latest validation exercises and in other studies of the BALB assay and the two protocols of the SHE cell test -namely, the need for an exogenous source of metabolic activation, and for the use of known/probable human carcinogens to effectively assess the predictivity of the cell transformation assays for human hazard. As discussed above, melphalan and o-toluidine are the only two known/probable human carcinogens included in the test chemical sets, and no additional metabolic activation has been used in any of the validation studies (7,(25)(26)(27)(28)(29)63).…”

Section: Discussionmentioning

confidence: 99%

“…A direct-acting bifunctional alkylating agent that binds to cellular macromolecules including DNA, RNA and protein. assays (25)(26)(27), nor in other recent validation studies of these test systems (28,29). The low numbers of chemicals that have been tested across the three main cell transformation assays is remarkable.…”

Section: Busulphan Y Y Y (Bhk)mentioning

confidence: 99%

Cell Transformation Assays: Are we Barking up the Wrong Tree?

Combes

2012

Altern Lab Anim

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There has been a current resurgence of interest in the use of cell transformation for predicting carcinogenicity, which is based mainly on rodent carcinogenicity data. In view of this renewed interest, this paper critically reviews the published literature concerning the ability of the available assays to detect IARC Group 1 agents (known human carcinogens) and Group 2A agents (probable human carcinogens). The predictivity of the available assays for human and rodent non-genotoxic carcinogens (NGCs), in comparison with standard and supplementary in vitro and in vivo genotoxicity tests, is also discussed. The principal finding is that a surprising number of human carcinogens have not been tested for cell transformation across the three main assays (SHE, Balb/c 3T3 and C3H10T1/2), confounding comparative assessment of these methods for detecting human carcinogens. This issue is not being addressed in the ongoing validation studies for the first two of these assays, despite the lack of any serious logistical issues associated with the use of most of these chemicals. In addition, there seem to be no plans for using exogenous bio-transformation systems for the metabolic activation of pro-carcinogens, as recommended in an ECVAM workshop held in 1999. To address these important issues, it is strongly recommended that consideration be given to the inclusion of more human carcinogens and an exogenous source of xenobiotic metabolism, such as an S9 fraction, in ongoing and future validation studies. While cell transformation systems detect a high level of NGCs, it is considered premature to rely only on this endpoint for screening for such chemicals, as recently suggested. This is particularly important, in view of the fact that there is still doubt as to the relevance of morphological transformation to tumorigenesis in vivo, and the wide diversity of potential mechanisms by which NGCs are known to act. Recent progress with regard to increasing the objectivity of scoring the transformed phenotype, and prospects for developing human cell-based transformation assays, are reviewed.

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“…In vitro data from CTAs with SHE ( LeBoeuf et al, 1996 , Maire et al, 2012b , Pant et al, 2012 ) and Balb/c 3T3 ( Atchison et al, 1982 , Dunkel et al, 1981 , Sakai and Sato, 1989 , Tanaka et al, 2012 ) cells were collected from the literature. The SHE assay is conducted with non-immortalized cells extracted from Syrian hamster embryos.…”

Section: Methodsmentioning

confidence: 99%

DNA adducts as link between in vitro and in vivo carcinogenicity – A case study with benzo[a]pyrene

Gerhards

Böhme

Schubert

et al. 2023

Current Research in Toxicology

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Prevalidation study of the Syrian hamster embryo (SHE) cell transformation assay at pH 7.0 for assessment of carcinogenic potential of chemicals

Cited by 14 publications

References 24 publications

A mechanistic evaluation of the Syrian hamster embryo cell transformation assay (pH 6.7) and molecular events leading to senescence bypass in SHE cells

A mechanistic evaluation of the Syrian hamster embryo cell transformation assay (pH 6.7) and molecular events leading to senescence bypass in SHE cells

Cell Transformation Assays: Are we Barking up the Wrong Tree?

DNA adducts as link between in vitro and in vivo carcinogenicity – A case study with benzo[a]pyrene

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