Mequindox Induced Genotoxicity and Carcinogenicity in Mice

Abstract

Mequindox (MEQ), acting as an inhibitor of deoxyribonucleic acid (DNA) synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM) mice (50 mice/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats

“…Together with genotoxic findings of MEQ, two primary metabolites of MEQ were concluded to be genotoxic in a battery of four different short-term tests, including mouse lymphoma assay (MLA), Ames test, chromosomal aberration assay and bone marrow erythrocyte micronucleus assay ( Liu et al, 2016 , 2017d ). A recent study suggested that MEQ induced genotoxicity and carcinogenicity in mice ( Liu et al, 2018b ). However, despite many years of usage in food producing animals, the toxic characteristics of MEQ, including its major toxic effects on the reproduction and development, had not been adequately investigated.…”

A Novel Metabolite as a Hapten to Prepare Monoclonal Antibodies for Rapid Screening of Quinoxaline Drug Residues

“…However, several studies have shown that Qx can cause toxic side effects such as trichothecation, photosensitivity, and adrenal cortical damage in livestock and poultry. More seriously, drug residues in animal-derived foods can pose a significant threat to the population directly consuming them [ 4 , 5 , 6 ]. According to the latest reports, the quinoxalines desoxymetabolites (desoxyquinoxalines, DQx) have the highest residues and have been identified as major toxicants.…”

Tracing major metabolites of quinoxaline‐1,4‐dioxides in abalone with high‐performance liquid chromatography tandem positive‐mode electrospray ionization mass spectrometry

“…Owing to their high antimicrobial activity, QdNOs have recently been applied in the aquaculture industry . However, QdNOs can induce severe toxic effects, including cytotoxicity, photoallergy, mutagenicity, and carcinogenicity . Consequently, close attention should be paid to exposure of QdNOs and the metabolites in diet.…”