Evaluation of modified bacterial mutagenicity assays for the genotoxicity testing of mineral oils.
A modified bacterial mutagenicity assay based on the Ames Salmonella/mammalian microsome test has been developed for application in the genotoxicity testing of mineral oils. The assay uses washed microsomes from rat liver in place of S9 fraction in order to increase the sensitivity of detection of genotoxicity. The modified assay was used to test a series of oils for which skin carcinogenicity bioassay data in mice were available. Oils were tested as emulsions in water using Tween 80 as a dispersant. A mutagenicity index for each oil was obtained using non-linear regression analysis of data from the dose-response curve. The results showed an empirical correlation between increasing mutagenicity index, carcinogenicity and the polycyclic aromatic hydrocarbon content of the oils. The washed-microsome assay was also compared with modified Ames assays developed by Blackburn et al. (Cell Biol. Toxicol., 1, 40, 1984; Cell Biol. Toxicol., 2, 63, 1986) which employed increased levels of S9 (rat and hamster liver) to test dimethyl sulphoxide extracts of oils. The washed-microsome assay can be used for the testing of whole oils rather than extracts which are necessary for the modified Ames assay. It is recognised that the determinants of carcinogenic activity in vivo include promoting activity which such assays are unable to detect. Nevertheless, such modified bacterial assays may be a useful prescreen since genotoxicity is recognised as a key initial step in carcinogenesis.
Brooks
T M
TM
Shell Research Ltd, Sittingbourne Research Centre, Sittingbourne, Kent, UK.
Priston
R A
RA
Wright
A S
AS
Watson
W P
WP
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005069:Evaluation Studies as Topic; D005260:Female; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000201:enzymology; D008899:Mineral Oil / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D004655:Emulsions; D009153:Mutagens; D008899:Mineral Oil