Urinary As species monomethylated MMAV percentage might incr
Urinary As species monomethylated (MMAV) percentage might increase and As species dimethylated (DMAV) percentage might decrease with increasing As exposure dosage (Lindberg et al., 2008). The limited methylation capacity associated with increased of As exposure dosage might probably explained through of the inhibition of the second methylation step by excessive InAs (Li et al., 2008). Nevertheless, in our study, the values of As methylated species followed the trend to increase DMA and MMA in subjects exposed to major As exposure dosage, there is no evidence that suggests a saturation in the As metabolic capacity, which could involve other explanatory mechanisms to this effect.
Regarding to effect of covariates tested as potential confounders in the logistic regression analysis in the present study, we perform interactions among GSTP1*age, GSTP1*BMI, and GSTP1*alcohol consumption. Although, in our finding the model had a moderate statistical strength, these type of interaction had been reported in the literature. BMI has been used as an indicator of nutritional status to evaluate the effect of this on As metabolism. Actually is known that the nutritional status play an important role in the regulation of As methylation and is related to health hazards. Some studies showed significant association with DMA positively and MMA negatively (Tseng et al., 2005) and others studies suggest two mechanisms; the exacerbation of nutritional status by As exposure and the effect of increased body fat on As accumulation in the high As exposure (Agusa et al., 2012). Nevertheless, the evidence is inconsistent, because other reports indicating no significant association of BMI with As chemicals i was reading this (Li et al., 2008; Lindberg et al., 2007). On the other hand, the alcohol consumption showed significant association with MMA and PMI, but it is an unclear relationship, due to that the alcohol effect was statistically significant in multiple regression analyses of PMI, only when was tested the interaction with GSTP1. However, some authors suggest as a potential mechanism that in presence of GST polymorphic genes is reduced the capacity to conjugate lipid peroxidation products, cytotoxic compounds, and free radicals generated during alcohol metabolism (Zhang et al., 2014; Grashow et al., 2014). Further, regarding to age, in the recent past has been suggested that children and young subjects may have a higher methylation capacity compared to adults (Chung et al., 2002). Likewise, other study show that the age of 63 years or older was significantly associated with a lower percentage of InAs and a higher percentage of DMA than those with an age <63 years, while the percentage of MMA, PMI and SMI were not significantly different between the two age groups (Chung et al., 2008). Due to contradictory outcomes associated with age, their effect on As metabolism needs to be confirmed. Furthermore, aging can probably be associated with a variety of functional changes in the organs involved in the metabolism or retention of the metabolites of As (Tseng, 2009).
Acknowledgements We would like to thank Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) in Colombia, Grant No. 110765843679; University of Chile in Chile, Grant No. 1140434; University of Cartagena in Colombia, Grant No. 252015 for the financial support. With a special thanks to Mike McGannon and Teresa Talsoudani for reading and correcting the language of the manuscript and Stephanía Contreras and Carla Miranda for their support in the University of Chile.
Value of the data
Data The data set shows the CYP450 enzymes and MGSTs activities in individual human liver microsomes (Table 1), the identified metabolism enzymes in human liver (Fig. S1), lung (Fig. S2), kidney (Fig. S3) and intestine (Fig. S4) microsomes are also reported.
Experimental design, materials and methods