2-Amino-3-methylimidazo[4,5-f]quinoline induces oxidative stress-mediated DNA damage and apoptosis in multi-organ of zebrafish

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of mutagenic/carcinogenic heterocyclic amines (HCAs) found mainly in well-cooked meats. As a common HCAs, IQ can pose a health risk to animals as well as humans. However, to date, few studies have explored IQ's toxic effects on systemic health, and its relevant mechanism of toxicity has not been elucidated. In this study, we for the first time determined IQ accumulation and investigated the tissue damage of developing zebrafish. Zebrafish at one-month post-fertilization were exposed to IQ (80 ng/mL) for 35 days. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis showed that IQ accumulated in multi-organ of zebrafish such as eye, spleen, gonad (ovary or testis), heart, intestine, kidney, muscle, liver, and brain. Our results showed that IQ exposure caused histopathological alterations in IQ-accumulated organs, which could compromise organ function. Exposure to IQ significantly inhibited antioxidant related indicators. Moreover, IQ exposure significantly increased mTOR gene levels. The immunohistochemical results further validated that IQ exposure tended to over activate mTOR. In addition, IQ exposure significantly reduced the expression of autophagy-related genes, and upregulated the expression of DNA damage and repair-related genes, which also detected the accumulation of fluorescence signal of DNA damage marker γ-H2AX. Furthermore, TUNEL assay showed that IQ exposure caused apoptosis. Our findings revealed that IQ could be taken up by developing zebrafish, and accumulate in multiple tissues, especially across the blood-brain barrier, accumulate in the brain, subsequently causing systemic tissue damage, urging us to pay attention to the control or intervention of IQ exposure and decreasing accumulated impairment to systemic health.