Chemical enhancement of SA7 virus transformation of hamster embryo cells: Evaluations by interlaboratory testing of diverse chemicals

Hatch, George G.; Anderson, Tara M.; Lubet, Ronald A.; Kouri, Richard E.; Putman, Donald L.; Cameron, J. W.; Nims, Raymond W.; Most, Bernard M.; Spalding, Judson W.; Tennant, R. W.; Schechtman, Leonard M.

doi:10.1002/em.2860080404

Cited by 33 publications

(9 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MP causes liver cancer in rats, but not mice (2), hamsters or guinea pigs (3). MP is negative in most routine genetic toxicology tests (4,5) but positive results have been reported in more specialized tests (6,7,8). MP has been reported to bind to DNA in vitro (9) but binding to DNA in vivo was not found (10,11).…”

Section: Introductionmentioning

confidence: 99%

Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene

Richardson¹,

Horn²,

Anderson

1994

Carcinogenesis

View full text Add to dashboard Cite

Dose-related effects of methapyrilene (MP) on protein modification and expression were examined using two-dimensional gel electrophoresis (2-D PAGE) coupled with computer analysis. Methapyrilene was administered ad libitum at doses of 0, 62.5, 125, 250 and 1000 p.p.m. to male F-344 rats for 12 weeks beginning at 8 weeks of age. Following treatment, livers were removed and frozen for 2-D PAGE analysis. Separation of hepatic proteins was conducted using ISO-DALT technology. Changes in abundance and modification of hepatic proteins were determined using the Kepler software package. Covalent modifications of three specific mitochondrial proteins were quantified using a charge modification index. Dose-response relationships were analyzed using Tukey's trend test. Results demonstrated that covalent modification of the three mitochondrial proteins was linearly related to dose and that a dose effect could be found at all dose levels in 2 out of 3 proteins. Two forms of change in protein expression were observed: (i) a dose-dependent change with effects at all doses and (ii) a change only at the toxic dose of 1000 p.p.m. MP. These results demonstrate a molecular effect of MP at doses that do not produce cellular responses including toxicity or increases in cell replication suggesting that these specific mitochondrial modifications are molecular dosimeters but are probably not direct factors and/or sufficient factors in carcinogenesis. This study also demonstrates the potential use of 2-D PAGE electrophoresis to delineate the effect of dose on expression of specific proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene

Richardson¹,

Horn²,

Anderson

1994

Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…Indeed, MP was reported to induce SHE cell transformation at concentrations ≥ 300 μM (i.e. 78 μg ml-1) (Hatch et al, 1986). Compound 2 had a greater transforming potency at low concentrations than at the highest ones.…”

Section: Discussionmentioning

confidence: 99%

“…MP has not been classified as a genotoxin based on conventional assays, but was positive in the in vitro SHE cell transformation assay (Hatch et al, 1986;Mirsalis, 1987). In 2011, Priestley et al (2011) investigated further the potential genotoxicity of MP using the in vitro Comet assay, and displayed significant increases in DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the genotoxic and carcinogenic potentials of 3‐aminothiophene derivatives using in vitro and in silico methodologies

Lepailleur

Bureau

Halm-Lemeille

et al. 2013

J of Applied Toxicology

View full text Add to dashboard Cite

Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3-amino-4-methylthiophene-2-carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure-toxicity relationships, we also studied two related compounds, namely the 3-amino 4-methylthiophene (2) and the 2-acetyl 4-chlorothiophene (3). Techniques employed to assess mutagenic and DNA-damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single-cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles.

show abstract

“…Many different types of chemical-induced genetic toxicity in cultured mammalian cells are detected optimally only when chemical treatments were moderately cytotoxic to the target cells, including point mutations (8) and chromosomal aberrations (9,10). Similarly, chemical enhancement of transforming activities in adenovirus-7 infected Syrian hamster embryo virus enhancement (SHE/SA7) transformation assay (11) has been optimally detected only when chemical treatments were moderately cytotoxic to the cells. Because genetic lesions are initiated in a single cell, the procedure used to assess cytotoxic damage must accurately reflect the survival and growth of a single altered cell within a population of many cells.…”

Section: Introductionmentioning

confidence: 99%

“…The prolonged selection period with ouabain was required because the cytotoxic effect of ouabain on high-density cultures of WT BALB/c-3T3 cells was relatively slow. After a total incubation period of 11 days, the culture vessels were fixed, stained, and OUA' colonies of cells were hand tabulated. The LD50 cytotoxic activity for individual chemicals was determined as described above.…”

Section: Co-culture Clonal Survival Assaymentioning

confidence: 99%

Transformation of BALB/c-3T3 Cells: III. Development of a Co-Culture Clonal Survival Assay for Quantification of Chemical Cytotoxicity in High-Density Cell Cultures

Matthews¹

1993

Environmental Health Perspectives

View full text Add to dashboard Cite

In contrast, chemical cytotoxic responses detected in the standard and co-culture assays differed by 2 10-fold for 11-aminoundecanoic acid, benzo[a]pyrene, cytosine arabinoside, and 3-methylcholanthrene and differed by >2-fold for 2-acetylaminofluorene and dimethylnitrosamine. Detection of 11-aminoundecanoic acid-induced transformation was shown to be dependent on selecting treatment doses from the co-culture assay data. Thus, this method permits more accurate assessment of both chemical-induced cytotoxicity and transformation.

show abstract

Chemical enhancement of SA7 virus transformation of hamster embryo cells: Evaluations by interlaboratory testing of diverse chemicals

Cited by 33 publications

References 10 publications

Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene

Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene

Assessment of the genotoxic and carcinogenic potentials of 3‐aminothiophene derivatives using in vitro and in silico methodologies

Transformation of BALB/c-3T3 Cells: III. Development of a Co-Culture Clonal Survival Assay for Quantification of Chemical Cytotoxicity in High-Density Cell Cultures

Contact Info

Product

Resources

About