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Are sulfite-oxidase-deficient animals unprotected against sulfite? — Attempts to detect cytogenetic effects
298 126 Renner, H.W., and J. Wever, Federal Research Centre for Nutrition, Engesserstrasse 20, D-75 Karlsruhe (F.R.G.) Are sulfite-oxidase-deficient animals unprotected against suifite? - detect cytogenetic effects
Attempts to
Sulfite used as food preservative is converted in the living organism by sulfite oxidase to sulfate. Mutagenic effects of sulfite have been reported in lower organism but not in mammals. Chinese hamsters and mice were made sulfite-oxidase deficient by raising them on a low-molybdenum diet and sodium-tungstate supplement. Enzyme activity in the liver was checked spectrophotometrically. Sulfite-treated fruit juices were given as single or repeated doses by stomach tube. Aqueous solutions of sulfite were administered parenterally as single or multiple injections up to toxic doses. For detection of possible cytogenetic effects 3 test systems were applied (on bone-marrow cells): (a) sister-chromatid exchange test, (b) chromosome aberration test, and (c) micronucleus test. The animal species used are representative for those with high (mouse) and low (Chinese hamster) sulfite-oxidase activities. With all 3 tests no induction of cytogenetic effects was observed indicating that no damage occurs on the chromosomal level in these animals, even when sulfiteoxidase activity was reduced to zero.
127 Richardson, C.R., and J.A. Styles, ICI, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire (Great Britain) The effect of sample size on the analysis of the eytogenetic effects of benzene inhalation by rats
Recent recommendations from EPA and OECD on testing procedures for mutagenicity have specified that in vivo cytogenetic analysis should be carried out on a minimum of 50 metaphase cells from bone marrow per animal and that each treatment group should contain at least 5 animals. This regime is at variance with the protocol previously used in our laboratory, based on the statistical argument of Evans and O'Riordan (Mutation Res., 31 (1975) 135-148), where 200 cells were analysed from each member of a treatment group containing 5 or more animals. Benzene was tested in rats by inhalation at levels of 0, 1, 10, 100 and 1000 ppm for 6 h. Animals were killed 24 h after exposure and the bone-marrow slides prepared by standard procedures. Metaphase chromosomes were analysed separately by the two protocols with the following results: 50 cells per animal, 0 ppm: 0.00 (12), 1 ppm: 0.69 (8), 10 ppm: 1.03" (8), 100 ppm: 1.07" (8), 1000 ppm: 2.62* (8). 200
Attempts to
Sulfite used as food preservative is converted in the living organism by sulfite oxidase to sulfate. Mutagenic effects of sulfite have been reported in lower organism but not in mammals. Chinese hamsters and mice were made sulfite-oxidase deficient by raising them on a low-molybdenum diet and sodium-tungstate supplement. Enzyme activity in the liver was checked spectrophotometrically. Sulfite-treated fruit juices were given as single or repeated doses by stomach tube. Aqueous solutions of sulfite were administered parenterally as single or multiple injections up to toxic doses. For detection of possible cytogenetic effects 3 test systems were applied (on bone-marrow cells): (a) sister-chromatid exchange test, (b) chromosome aberration test, and (c) micronucleus test. The animal species used are representative for those with high (mouse) and low (Chinese hamster) sulfite-oxidase activities. With all 3 tests no induction of cytogenetic effects was observed indicating that no damage occurs on the chromosomal level in these animals, even when sulfiteoxidase activity was reduced to zero.
127 Richardson, C.R., and J.A. Styles, ICI, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire (Great Britain) The effect of sample size on the analysis of the eytogenetic effects of benzene inhalation by rats
Recent recommendations from EPA and OECD on testing procedures for mutagenicity have specified that in vivo cytogenetic analysis should be carried out on a minimum of 50 metaphase cells from bone marrow per animal and that each treatment group should contain at least 5 animals. This regime is at variance with the protocol previously used in our laboratory, based on the statistical argument of Evans and O'Riordan (Mutation Res., 31 (1975) 135-148), where 200 cells were analysed from each member of a treatment group containing 5 or more animals. Benzene was tested in rats by inhalation at levels of 0, 1, 10, 100 and 1000 ppm for 6 h. Animals were killed 24 h after exposure and the bone-marrow slides prepared by standard procedures. Metaphase chromosomes were analysed separately by the two protocols with the following results: 50 cells per animal, 0 ppm: 0.00 (12), 1 ppm: 0.69 (8), 10 ppm: 1.03" (8), 100 ppm: 1.07" (8), 1000 ppm: 2.62* (8). 200