Morphological transformation and effect on gap junction intercellular communication in Syrian hamster embryo cells as
E Rivedal1, S O Mikalsen, T Sanner
1Department of Environmental and Occupational Cancer, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310, Oslo, Norway. edgar.rivedal@labmed.uio.no
Abstract:
A large fraction of chemicals observed to cause cancer in experimental animals is devoid of mutagenic activity. It is therefore of importance to develop methods that can be used to detect and study environmental carcinogenic agents that do not interact directly with DNA. Previous studies have indicated that induction of in vitro cell transformation and inhibition of gap junction intercellular communication are endpoints that could be useful for the detection of non-genotoxic carcinogens. In the present work, 13 compounds [chlordane, Arochlor 1260, di(2-ethylhexyl)phthalate, 1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane, limonene, sodium fluoride, ethionine, o-anisidine, benzoyl peroxide, o-vanadate, phenobarbital, 12-O-tetradecanoylphorbol 13-acetate and clofibrate] have been tested for their ability to induce morphological transformation and affect intercellular communication in Syrian hamster embryo cells. The substances were selected on the basis of being proven or suspected non-genotoxic carcinogens, and thus difficult to detect in short-term tests. The data show that nine of the 13 compounds induced morphological transformation, and seven of the 13 inhibited intercellular communication in hamster embryo cells. Taken together, 12 of the 13 substances either induced transformation or caused inhibition of communication. The data suggest that the combined use of morphological transformation and gap junction intercellular communication in Syrian hamster embryo cells may be beneficial when screening for non-genotoxic carcinogens.
Insights
Detecting non-genotoxic carcinogens is crucial. This study shows that testing for cell transformation and inhibited communication in hamster cells effectively identifies these difficult-to-detect environmental agents.
Area of Science:
- Toxicology
- Carcinogenesis
- Cell Biology
Background:
- Many carcinogens do not directly damage DNA, posing detection challenges.
- Non-genotoxic carcinogens require alternative screening methods beyond mutagenicity tests.
- Cell transformation and gap junction communication are potential indicators for non-genotoxic carcinogens.
Purpose of the Study:
- To evaluate the efficacy of in vitro cell transformation and gap junction intercellular communication assays.
- To screen 13 known or suspected non-genotoxic carcinogens using these endpoints.
- To determine if these assays can detect environmental agents that don't interact with DNA.
Main Methods:
- Utilized Syrian hamster embryo cells for in vitro testing.
- Assessed the induction of morphological cell transformation by chemical compounds.
- Measured the inhibition of gap junction intercellular communication (GJIC) following compound exposure.
Main Results:
- Nine out of 13 tested compounds induced morphological transformation.
- Seven out of 13 compounds inhibited intercellular communication.
- Twelve of the 13 non-genotoxic carcinogens tested showed positive results in at least one assay.
Conclusions:
- Combined assays for cell transformation and GJIC are effective for detecting non-genotoxic carcinogens.
- These methods offer a valuable screening approach for environmental carcinogens lacking mutagenic activity.
- The study supports the use of these endpoints for identifying chemicals that pose cancer risks through non-DNA-interactive mechanisms.
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