Sanitization of the cellular nucleotide pools from mutagenic base analogues is necessary for the accuracy of transcription and replication of genetic material and plays a substantial role in cancer prevention. The undesirable mutagenic, recombinogenic, and toxic incorporation of purine base analogues [i.e., ITP, dITP, XTP, dXTP, or 6-hydroxylaminopurine (HAP) deoxynucleoside triphosphate] into ...

In the mouse genome, we found one processed Itpa gene-like sequence and two processed Itpa pseudogenes as well as the Itpa gene itself with introns, located on chromosome 2F3, which was isolated by a retro-recombination method. We also identified three types (A, B, C) of Itpa transcripts in mouse tissues. The processed Itpa gene-like sequence located on chromosome 2E1 has a complete open readin...

Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa(-) mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa(-) embryos than in wild-type embryos. Therefore, we examined the effects of ITPA deficiency on mouse embryo...

Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results i...

Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The g...

Inosine triphosphate pyrophosphatase (ITPA protein) (EC 3.6.1.19) hydrolyzes deaminated purine nucleoside triphosphates, such as ITP and dITP, to their corresponding purine nucleoside monophosphate and pyrophosphate. In mammals, this enzyme is encoded by the Itpa gene. Using the Itpa gene-disrupted mouse as a model, we have elucidated the biological significance of the ITPA protein and its subs...

Ribavirin remains an important component of hepatitis C treatment in certain clinical scenarios, but it causes hemolytic anemia. A quantitative understanding of the ribavirin exposure-anemia relationship is important in dose individualization/optimization. We developed a model relating ribavirin triphosphate (RTP) exposure in red blood cells (RBCs), RBC lifespan, feedback regulation of RBC prod...

BACKGROUND Severe anemia is a common side effect of Pegylated Interferon + Ribavirin (PR) and Telaprevir (TVR) in hepatitis C virus (HCV) genotype 1 patients with advanced fibrosis or cirrhosis (F3-F4). Inosine triphosphatase (ITPA) genetic variants are associated with RBV- induced anemia and dose reduction. AIM To test the association of ITPA polymorphisms rs1127354 and rs7270101 with hemogl...

In this study, we propose an IT-based peer assessment (ITPA) for enhancing interaction and feedback in universities’ large-scale lectures. These lectures often lack interaction and feedback, and focus on mainly imparting factual knowledge. Hence, these formats often cannot go beyond the basic cognitive levels of educational objectives. Using the ITPA within the learning process helps integratin...

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically import...