ABSTRACT
Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
ABSTRACT
Calbindin 9K(CaBP-9k) and Calbindin 28K(CaBP-28k),vitamin D dependent calcium binding protein (CaBP),play an important role in the the process of active transport of calcium.Research has shown that vitamin D can increase the expression of calcium binding protein,which can promote the absorption of calcium ions.Vitamin D deficiency and calcium binding protein could cause disorders of calcium homeostasis,such as hypocalcemia,rickets,osteoporosis and many other diseases.This review summarizes the studies of structure and distribution of CaBP and the mechanism of vitamin D in regulation of CaBP,which might provide new strategies for the prevention and treatment of paraplasia ossium.