Cytidine deaminase activity in abnormal pregnancy

Okamura, Takashi; Kigasawa, K.; Takeuchi, T.; Ohta, Chikako

doi:10.1016/0020-7292(93)90154-o

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…CDA activity was measured spectrophotometrically as previously described 25,35,36 using a simple and rapid high-performance liquid chromatography-based method derived from Okamura et al After overnight incubation of serum samples, CDA activity was evaluated on the conversion of cytidine to uridine with ammonium release. CDA activity was finally expressed as units per milligram proteins, with 1 U = 10 -4 mmol ammonium released/min.…”

Section: Cytidine Deaminase Phenotypic Assaymentioning

confidence: 99%

High-Resolution Melting Analysis of Sequence Variations in the Cytidine Deaminase Gene (CDA) in Patients With Cancer Treated With Gemcitabine

Raynal¹,

Ciccolini²,

Mercier³

et al. 2010

Therapeutic Drug Monitoring

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Gemcitabine (2',2'-difluorodeoxycytidine) is a major antimetabolite cytotoxic drug with a wide spectrum of activity against solid tumors. Hepatic elimination of gemcitabine depends on a catabolic pathway through a deamination step driven by the enzyme cytidine deaminase (CDA). Severe hematologic toxicity to gemcitabine was reported in patients harboring genetic polymorphisms in CDA gene. High-resolution melting (HRM) analysis of polymerase chain reaction amplicon emerges today as a powerful technique for both genotyping and gene scanning strategies. In this study, 46 DNA samples from gemcitabine-treated patients were subjected to HRM analysis on a LightCycler 480 platform. Residual serum CDA activity was assayed as a surrogate marker for the overall functionality of this enzyme. Genotyping of three well-described single nucleotide polymorphisms in coding region (c.79A>C, c.208G>A and c.435C>T) was successfully achieved by HRM analysis of small polymerase chain reaction fragments, whereas unknown single nucleotide polymorphisms were searched by a gene scanning strategy with longer amplicons (up to 622 bp). The gene scanning strategy allowed us to find a new intronic mutation c.246+37G>A in a female patient displaying marked CDA deficiency and who had an extreme toxic reaction with a fatal outcome to gemcitabine treatment. Our work demonstrates that HRM-based methods, owing to their simplicity, reliability, and speed, are useful tools for diagnosis of CDA deficiency and could be of interest for personalized medicine.

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Section: Cytidine Deaminase Phenotypic Assaymentioning

confidence: 99%