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... the shortened gestational length. In addition, organic solvent exposure, even at a level at leastsfive times lower than the safety level required by the Occupational Safety and HealthsAdministration,=-=[33]-=- was significantly related to the shortened gestation. When considering bothsorganic solvents exposure and combined maternal-infant genotypes, the largest associations weresfound among exposed women w...

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...hsas preterm birth is considered a major public health concern because of its high prevalence,sassociation with mortality and morbidity, and increased cost of hospitalization and long-termsdisability.=-=[2]-=- Morken suggested that the association between birth weight lower than the populationsmean and spontaneous preterm birth may be evident for all gestational age groups.[3] The etiologysof shortened ges...

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...rth weight,[15] shortened gestational age[6] and an increased risk for congenitalsanomalies.[16]sHowever, not all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,=-=[6,17]-=- and several studies have suggested potential reasons lie in maternalsand infant genetic susceptibility.[16,18,19] Metabolism of organic solvents includes 2 phases ofsdetoxification: phase I, in which...

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...ant genetic susceptibility tosorganic solvents exposure in relation to gestational age, this susceptibility is biologicallysplausible. Benzene suggested specifically as a potential reproductive toxin.=-=[9,11]-=- Its toxicity wassproduced by one or more metabolites of benzene, in particular the covalent binding to cellularsmacromolecules, rather than by benzene itself, the intermediates probably being more to...

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...l/Val462 together in the later data analysis due to the small number of subjectsswith Val/Val462 genotype.sThe detailed method on detection of the GSTT1 and GSTM1 polymorphisms can be foundselsewhere.=-=[24,26]-=- This method is only able to detect the present (at least 1 allele present, AA or Aa)sor absent (complete deletion of both alleles, aa) genotype.sPreviously sequenced genomic DNA samples were used as ...

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...by http://oem.bmj.com/Downloaded froms15sthe original form.[34] Some animal and human studies observed that benzene could be transferredsthrough placenta and further affect the development of infants.=-=[35,36]-=- The cytochrome P450 familysand the glutathione S-transferases (GSTs) serve as the major enzymes in the 2-phase detoxificationsof organic solvents. Alexandrov et al found that the levels of benzo(a)py...

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...tion and long-termsdisability.[2] Morken suggested that the association between birth weight lower than the populationsmean and spontaneous preterm birth may be evident for all gestational age groups.=-=[3]-=- The etiologysof shortened gestational age was largely unknown, but both environmental and genetic factors andstheir interactions may play important roles.[4-6]sFor the general population, organic sol...

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...e was largely unknown, but both environmental and genetic factors andstheir interactions may play important roles.[4-6]sFor the general population, organic solvents are widespread at work and at home.=-=[7,8]-=-sBenzene,[9-11] toluene[12,13] and related compounds have been identified as potential reproductivestoxins. Although exposure levels in most modern industries is far below the limit recommended bysthe...

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...s between genetic susceptibility in these genes and reproductive outcomes includingsgestational age,[6] birth weight,[17] intrauterine fetal growth restriction[27]andssmall-for-gestational-age births.=-=[28]-=-sMost studies have examined only maternal genes while neglecting fetal genotype and combinedsmaternal-fetal genetic susceptibility, and little information is available on the associations ofscombined ...

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...ed bysthe Occupational Safety and Health Administration,[14] several studies suggested that benzenesexposure even at low level might link to adverse reproductive outcomes such as spontaneoussabortion,=-=[11]-=- low birth weight,[15] shortened gestational age[6] and an increased risk for congenitalsanomalies.[16]sHowever, not all women exposed to organic solvents during pregnancy have adversesreproductive ou...

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...onjugated with certain endogenoussfunctional groups such as glutathione, sulfate, glucuronide, and amino acids. Thus, the end productsbecomes a stable hydrophilic compound that can easily be excreted.=-=[20]-=- Benzene-induced toxicitysin animals is clearly mediated by its metabolism.[21] However, if there are genetic variationssoccurring in the metabolic enzymes, normal metabolic process will be disturbed....

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...ive outcomes ofsorganic solvents exposure are in part attributable to different maternal and infant genotypessassociated with these enzymes. CYP1A1 MspI variant genotypes may increase enzyme activity,=-=[41]-=-swhile the deletion type of GSTT1 leads to an absence of enzyme activity.[32,41] Both CYP1A1sgenes and GSTs (GSTT1 and GSTM1) genes are highly polymorphic in our study population.sThus, we may suggest...

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...oth environmental and genetic factors andstheir interactions may play important roles.[4-6]sFor the general population, organic solvents are widespread at work and at home.[7,8]sBenzene,[9-11] toluene=-=[12,13]-=- and related compounds have been identified as potential reproductivestoxins. Although exposure levels in most modern industries is far below the limit recommended bysthe Occupational Safety and Healt...

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...nsof organic solvents. Alexandrov et al found that the levels of benzo(a)pyrene diol-epoxide-DNAsadducts and bulky DNA adducts were significantly and positively correlated with CYP1A1senzyme activity.=-=[37]-=- The GSTT1 enzyme is important in protecting against certain genotoxicsdamages, such as sister chromatid exchanges and the formation of hemoglobin adducts.[38,39]sFurthermore, infant with growth retar...

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...ion,[14] several studies suggested that benzenesexposure even at low level might link to adverse reproductive outcomes such as spontaneoussabortion,[11] low birth weight,[15] shortened gestational age=-=[6]-=- and an increased risk for congenitalsanomalies.[16]sHowever, not all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,[6,17] and several studies have suggested po...

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...performed the occupational exposure assessment were memberssof our research team, had no relationship with the Petrochemical Company.sGenotypingsWe detected CYP1A1 Msp according to Kawajiri’s method,=-=[32]-=- which is able to detect all 3sgenotypes for the polymorphism: T/T6235 (homozygous wild type), T/C6235 (heterozygoussvariant type), and C/C6235 (homozygous variant type). We combined T/C6235 and C/C62...

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...oth environmental and genetic factors andstheir interactions may play important roles.[4-6]sFor the general population, organic solvents are widespread at work and at home.[7,8]sBenzene,[9-11] toluene=-=[12,13]-=- and related compounds have been identified as potential reproductivestoxins. Although exposure levels in most modern industries is far below the limit recommended bysthe Occupational Safety and Healt...

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...all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,[6,17] and several studies have suggested potential reasons lie in maternalsand infant genetic susceptibility.=-=[16,18,19]-=- Metabolism of organic solvents includes 2 phases ofsdetoxification: phase I, in which the original nonpolar compound becomes polar and reactive, andsphase II, in which the transformed polar compound ...

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...nd GSTT genes are highly polymorphic in the population,[22-24] which isspartly responsible for the interindividual differences in the metabolic activation and detoxificationspathways of these enzymes.=-=[23,25,26]-=- Besides, molecular epidemiological studies have demonstratedsassociations between genetic susceptibility in these genes and reproductive outcomes includingsgestational age,[6] birth weight,[17] intra...

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...by http://oem.bmj.com/Downloaded froms15sthe original form.[34] Some animal and human studies observed that benzene could be transferredsthrough placenta and further affect the development of infants.=-=[35,36]-=- The cytochrome P450 familysand the glutathione S-transferases (GSTs) serve as the major enzymes in the 2-phase detoxificationsof organic solvents. Alexandrov et al found that the levels of benzo(a)py...

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... Safety and Health Administration,[14] several studies suggested that benzenesexposure even at low level might link to adverse reproductive outcomes such as spontaneoussabortion,[11] low birth weight,=-=[15]-=- shortened gestational age[6] and an increased risk for congenitalsanomalies.[16]sHowever, not all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,[6,17] and seve...

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...e, glucuronide, and amino acids. Thus, the end productsbecomes a stable hydrophilic compound that can easily be excreted.[20] Benzene-induced toxicitysin animals is clearly mediated by its metabolism.=-=[21]-=- However, if there are genetic variationssoccurring in the metabolic enzymes, normal metabolic process will be disturbed. Some toxicsadducts generate and do harm to DNA and chromosomes in the placenta...

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...nd GSTT genes are highly polymorphic in the population,[22-24] which isspartly responsible for the interindividual differences in the metabolic activation and detoxificationspathways of these enzymes.=-=[23,25,26]-=- Besides, molecular epidemiological studies have demonstratedsassociations between genetic susceptibility in these genes and reproductive outcomes includingsgestational age,[6] birth weight,[17] intra...

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...y correlated with CYP1A1senzyme activity.[37] The GSTT1 enzyme is important in protecting against certain genotoxicsdamages, such as sister chromatid exchanges and the formation of hemoglobin adducts.=-=[38,39]-=-sFurthermore, infant with growth retardation and/or premature birth were more likely to haveshigher frequencies of adducts, DNA damage and chromosomal aberrations in the placenta andsfetal cells.[40] ...

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...teraction of the 4 genes was determined.sgroup.bmj.com on May 10, 2016 - Published by http://oem.bmj.com/Downloaded froms3sINTRODUCTIONsThe duration of gestation is a key predictor of infant survival.=-=[1]-=- Shortened gestational age suchsas preterm birth is considered a major public health concern because of its high prevalence,sassociation with mortality and morbidity, and increased cost of hospitaliza...

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...e was largely unknown, but both environmental and genetic factors andstheir interactions may play important roles.[4-6]sFor the general population, organic solvents are widespread at work and at home.=-=[7,8]-=-sBenzene,[9-11] toluene[12,13] and related compounds have been identified as potential reproductivestoxins. Although exposure levels in most modern industries is far below the limit recommended bysthe...

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...ounds have been identified as potential reproductivestoxins. Although exposure levels in most modern industries is far below the limit recommended bysthe Occupational Safety and Health Administration,=-=[14]-=- several studies suggested that benzenesexposure even at low level might link to adverse reproductive outcomes such as spontaneoussabortion,[11] low birth weight,[15] shortened gestational age[6] and ...

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...osure even at low level might link to adverse reproductive outcomes such as spontaneoussabortion,[11] low birth weight,[15] shortened gestational age[6] and an increased risk for congenitalsanomalies.=-=[16]-=-sHowever, not all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,[6,17] and several studies have suggested potential reasons lie in maternalsand infant genetic s...

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...all women exposed to organic solvents during pregnancy have adversesreproductive outcomes,[6,17] and several studies have suggested potential reasons lie in maternalsand infant genetic susceptibility.=-=[16,18,19]-=- Metabolism of organic solvents includes 2 phases ofsdetoxification: phase I, in which the original nonpolar compound becomes polar and reactive, andsphase II, in which the transformed polar compound ...

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...nd GSTT genes are highly polymorphic in the population,[22-24] which isspartly responsible for the interindividual differences in the metabolic activation and detoxificationspathways of these enzymes.=-=[23,25,26]-=- Besides, molecular epidemiological studies have demonstratedsassociations between genetic susceptibility in these genes and reproductive outcomes includingsgestational age,[6] birth weight,[17] intra...

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...cal studies have demonstratedsassociations between genetic susceptibility in these genes and reproductive outcomes includingsgestational age,[6] birth weight,[17] intrauterine fetal growth restriction=-=[27]-=-andssmall-for-gestational-age births.[28]sMost studies have examined only maternal genes while neglecting fetal genotype and combinedsmaternal-fetal genetic susceptibility, and little information is a...

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...lude benzene, toluene, styrene, and their derivatives. In our study period, thestime-weighted average for benzene during an 8-hour shift for exposed workers ranged from 0.017sppm to 0.191 ppm at BYPC.=-=[29]-=- The Occupational Safety and Health Administration limit is 1 ppmsas an 8-hour time-weighted average.[14] The BYPC Staff Hospital, the only regional hospital thatsserves the community, provides prenat...

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...d as exposedsgroup. Finally, women who were not exposed to any solvents were classified as unexposed.sFurther details of the exposure assessment method and validation results are described elsewhere.s=-=[31]-=- The industrial hygienists who performed the occupational exposure assessment were memberssof our research team, had no relationship with the Petrochemical Company.sGenotypingsWe detected CYP1A1 Msp ...

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...arsmacromolecules, rather than by benzene itself, the intermediates probably being more toxic thansgroup.bmj.com on May 10, 2016 - Published by http://oem.bmj.com/Downloaded froms15sthe original form.=-=[34]-=- Some animal and human studies observed that benzene could be transferredsthrough placenta and further affect the development of infants.[35,36] The cytochrome P450 familysand the glutathione S-transf...

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...y correlated with CYP1A1senzyme activity.[37] The GSTT1 enzyme is important in protecting against certain genotoxicsdamages, such as sister chromatid exchanges and the formation of hemoglobin adducts.=-=[38,39]-=-sFurthermore, infant with growth retardation and/or premature birth were more likely to haveshigher frequencies of adducts, DNA damage and chromosomal aberrations in the placenta andsfetal cells.[40] ...

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...8,39]sFurthermore, infant with growth retardation and/or premature birth were more likely to haveshigher frequencies of adducts, DNA damage and chromosomal aberrations in the placenta andsfetal cells.=-=[40]-=- Interindividual differences in susceptibility to adverse reproductive outcomes ofsorganic solvents exposure are in part attributable to different maternal and infant genotypessassociated with these e...