关键词: Colon Glandular stomach Liver Micronucleus assay Potassium bromate Repeated dose study

Mesh : Administration, Oral Age Factors Animals Body Weight / drug effects Bone Marrow / drug effects pathology Bromates / toxicity Carcinogens / toxicity Chromosome Aberrations / drug effects Colon / drug effects Cooperative Behavior Dose-Response Relationship, Drug Drug Administration Schedule Hepatocytes / drug effects Humans Japan Kidney / drug effects pathology Liver / drug effects Male Micronucleus Tests Organ Specificity Rats Rats, Sprague-Dawley Societies, Pharmaceutical Stomach / drug effects pathology

来  源:   DOI:10.1016/j.mrgentox.2014.03.002   PDF(Sci-hub)

Abstract:
The food additive potassium bromate (KBrO3) is known as a renal carcinogen and causes chromosomal aberrations in vitro without metabolic activation and in vivo in hematopoietic and renal cells. As a part of a collaborative study by the Mammalian Mutagenicity Study group, which is a subgroup of the Japanese Environmental Mutagen Society, we administered KBrO3 to rats orally for 4, 14, and 28 days and examined the micronucleated (MNed) cell frequency in the liver, glandular stomach, colon, and bone marrow to confirm whether the genotoxic carcinogen targeting other than liver and gastrointestinal (GI) tract was detected by the repeated dose liver and GI tract micronucleus (MN) assays. In our study, animals treated with KBrO3 showed some signs of toxicity in the kidney and/or stomach. KBrO3 did not increase the frequency of MNed cells in the liver and colon in any of the repeated dose studies. However, KBrO3 increased the frequency of MNed cells in the glandular stomach and bone marrow. Additionally, the MNed cell frequency in the glandular stomach was not significantly affected by the difference in the length of the administration period. These results suggest that performing the MN assay using the glandular stomach, which is the first tissue to contact agents after oral ingestion, is useful for evaluating the genotoxic potential of chemicals and that the glandular stomach MN assay could be integrated into general toxicity studies.
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