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Although arsenic has shown remarkable therapeutic efficacy in patients with acute promyelocytic leukemia (APL), its side effects are rarely reported. In this article, the associations among urinary arsenic profiles, hematological and biochemical values, and 3 AS3MT genotypes (rs3740392, rs3740390, and rs11191439) were evaluated in 50 APL patients treated with arsenic trioxide (As2O3). Results revealed the levels of serum enzymes (ALT, AST, and GGT), GLU and the count of WBC and NEUT#, which were markers of hepatic damage, diabetes and leukocytosis, respectively, were increased significantly 10 days after the administration of As2O3. The percentages of dimethylated arsenic (DMA) and the secondary methylation index (SMI, DMA/MMA) were negatively associated with the levels of ALT and AST. Patients with the AS3MT rs3740390 TC or TT genotype, compared with rs3740390 CC genotype, had significantly higher levels of DMA%, SMI and significantly lower levels of ALT and AST. Furthermore, the frequency for the heterozygous variant of rs11191439 was absolute low (N = 1). For rs3740392, no statistical differences were noted in urinary arsenic profiles and hematological and biochemical values in individuals with different genotypes. These results indicate that inherent genetic information of the AS3MT rs3740390 genotypes is a novel predicted or evaluated target for As2O3-induced side effects and therapeutic efficacy for the treatment of APL.
This article was published in the following journal.
Name: Toxicological sciences : an official journal of the Society of Toxicology
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A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)
The complete summaries of the frequencies of the values or categories of a measurement made on a group of items, a population, or other collection of data. The distribution tells either how many or what proportion of the group was found to have each value (or each range of values) out of all the possible values that the quantitative measure can have.
An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases.
Defective metabolism leading to fat maldistribution in patients infected with HIV. The etiology appears to be multifactorial and probably involves some combination of infection-induced alterations in metabolism, direct effects of antiretroviral therapy, and patient-related factors.
Disorders associated with acute or chronic exposure to compounds containing ARSENIC (ARSENICALS) which may be fatal. Acute oral ingestion is associated with gastrointestinal symptoms and an encephalopathy which may manifest as SEIZURES, mental status changes, and COMA. Chronic exposure is associated with mucosal irritation, desquamating rash, myalgias, peripheral neuropathy, and white transverse (Mees) lines in the fingernails. (Adams et al., Principles of Neurology, 6th ed, p1212)
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