Dataset Information

In vitro analysis of factors influencing CYP1A2 expression as potential determinants of interindividual variation.

ABSTRACT: Individual differences in drug metabolism contribute to interindividual variation that characterizes responses to drugs and risk in exposure to foreign chemicals. Large individual differences are found in expression levels of CYP1A2, a major drug-metabolizing enzyme. Underlying causes for this variation are not well understood. Several factors, including tobacco smoking, consumption of cruciferous vegetables, and sex, have been associated with modulating CYP1A2 expression. To understand factors regulating expression of CYP1A2 in establishing a causal relationship, this study examined effects of cigarette smoke condensate (CSC), indole-3-carbinol (I3C), and 17?-estradiol (estradiol) on CYP1A2 expression in in vitro systems using human liver and lung cells. Treatment with CSC (2-25 ?g/mL) significantly increased levels of CYP1A2 in six cell lines examined, in a concentration- and time-dependent manner. Fold changes in expression levels relative to controls varied among cell lines. CYP1A2 enzymatic activity also increased with CSC exposure. Treatment of H1299 and HepB3 cells with dietary agent I3C (50 and 100 ?mol/L) increased CYP1A2 expression. In human cell lines H1299 and H1395, treatment with estradiol (10 and 100 nmol/L) significantly reduced expression of CYP1A2. Using ChIP assays, effects of CSC on histone modifications were analyzed. Increases in H3K4me3 and H4K16ac were observed at several segments in the CYP1A2 gene, whereas H3K27me3 decreased, following CSC treatment. These results suggest that CYP1A2 expression is affected epigenetically by CSC. Additional studies will be needed to further establish regulatory mechanisms underlying effects of various environmental, dietary, and endogenous factors on CYP1A2 expression in better predicting individual variation.

SUBMITTER: Xie C

PROVIDER: S-EPMC5368963 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In vitro analysis of factors influencing CYP1A2 expression as potential determinants of interindividual variation.

Xie ChengHui C Pogribna Marta M Word Beverly B Lyn-Cook Lascelles L Lyn-Cook Beverly D BD Hammons George J GJ

Pharmacology research & perspectives 20170302 2

Individual differences in drug metabolism contribute to interindividual variation that characterizes responses to drugs and risk in exposure to foreign chemicals. Large individual differences are found in expression levels of CYP1A2, a major drug-metabolizing enzyme. Underlying causes for this variation are not well understood. Several factors, including tobacco smoking, consumption of cruciferous vegetables, and sex, have been associated with modulating CYP1A2 expression. To under ...[more]

PMID: 28357125

Similar Datasets

Project description:Understanding the factors shaping human crania has long been a goal of biological anthropology, and climate, diet, and population history are three of the most well-established influences. The effects of these factors are, however, rarely compared within a single, variable population, limiting interpretations of their relative contribution to craniofacial form. Jomon prehistoric foragers inhabited Japan throughout its climatic and ecological range and developed correspondingly varied modes of subsistence. We have previously demonstrated that a large sample of Jomon crania showed no clear climatic pattern; here, we examine variation in Jomon crania in more detail to determine if dietary factors and/or population history influence human intrapopulation variation at this scale. Based on well-established archaeological differences, we divide the Jomon into dietary groups and use geometric morphometric methods to analyse relationships between cranial shape, diet, and population history. We find evidence for diet-related influences on the shape of the neurocranium, particularly in the temporalis region. These shape differences may be interpreted in the context of regional variation in the biomechanical requirements of different diets. More experimental biomechanical and nutritional evidence is needed, however, to move suggested links between dietary content and cranial shape from plausible to well-supported. In contrast with the global scale of human variation, where neutral processes are the strongest influence on cranial shape, we find no pattern of population history amongst individuals from these Jomon sites. The determinants of cranial morphology are complex and the effect of diet is likely mediated by factors including sex, social factors, and chronology. Our results underline the subtlety of the effects of dietary variation beyond the forager/farmer dichotomy on cranial morphology and contribute to our understanding of the complexity of selective pressures shaping human phenotypes on different geographic scales.Supplementary informationThe online version contains supplementary material available at 10.1007/s12520-023-01901-6.

Dataset Information

In vitro analysis of factors influencing CYP1A2 expression as potential determinants of interindividual variation.

Publications

In vitro analysis of factors influencing <i>CYP1A2</i> expression as potential determinants of interindividual variation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets