In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line.
A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an 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/10T(1/2) 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. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.
Kowalski
L A
LA
Vera Genics Ltd., Vancouver, British Columbia, Canada. kowalski@attglobal.net
Laitinen
A M
AM
Mortazavi-Asl
B
B
Wee
R K
RK
Erb
H E
HE
Assi
K P
KP
Madden
Z
Z
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002417:Cattle; D002460:Cell Line; D018920:Coculture Techniques; D006224:Cricetinae; D004279:DNA, Viral / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D015203:Reproducibility of Results
D002273:Carcinogens; D004279:DNA, Viral