Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm delivery.

Objective: To determine whether mid-pregnancy levels of angiogenic markers were associated with increased risk of preterm delivery (PTD).

Methods: We studied a subcohort from the Pregnancy Outcomes and Community Health Study for whom mid-pregnancy angiogenic markers (soluble fms-like tyrosine kinase-1 [sFlt-1], soluble endoglin [sEng] and placental growth factor [PlGF]) and covariate data were available (N = 1301). Angiogenic marker levels were grouped as high/not high (sFlt-1 and sEng), low/not low (PlGF) and high/intermediate/low (sFlt-1).

Proteomic analysis of the effects of the immunomodulatory mycotoxin deoxynivalenol.

The mycotoxin deoxynivalenol (DON) contaminates cereals worldwide and is a common contaminant in the Western European diet. At high doses, DON induces acute gastrointestinal toxicity; chronic, low-dose effects in humans are not well described, but immunotoxicity has been reported. In this study, 2-DE was used to identify proteomic changes in human B (RPMI1788) and T (JurkatE6.

Midpregnancy levels of angiogenic markers in relation to maternal characteristics.

Objective: The purpose of this study was to describe relations among maternal demographic and lifestyle characteristics and midpregnancy levels of angiogenic markers (soluble Fms-like tyrosine kinase-1, placental growth factor, soluble endoglin).

Study Design: In a large pregnancy cohort, linear models were used to evaluate relations among maternal characteristics and midpregnancy angiogenic markers with and without covariate adjustment. Associations were examined in a subcohort that included term and preterm deliveries (n = 1302) and among "normal" term pregnancies (n = 668).

Blood cadmium levels in women of childbearing age vary by race/ethnicity.

The heavy metal cadmium (Cd) is long-lived in the body and low-level cumulative exposure, even among non-smokers, has been associated with changes in renal function and bone metabolism. Women are more susceptible to the adverse effects of Cd and have higher body burdens. Due to increased dietary absorption of Cd in menstruating women and the long half-life of the metal, reproductive age exposures are likely important contributors to overall body burden and disease risk.

Adverse effects of low level heavy metal exposure on male reproductive function.

Lead, cadmium, mercury, and arsenic, often referred to as "heavy metals", are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. We review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies.

DNA sequence context affects repair of the tobacco-specific adduct O(6)-[4-Oxo-4-(3-pyridyl)butyl]guanine by human O(6)-alkylguanine-DNA alkyltransferases.

The repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) protects cells from the mutagenic and carcinogenic effects of alkylating agents by removing O(6)-alkylguanine adducts from DNA. Recently, we established that AGT protects against the mutagenic effects of pyridyloxobutylation resulting from the metabolic activation of the tobacco-specific nitrosamines (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine by repairing O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine (O(6)-pobG). There have been several epidemiologic studies examining the association between the I143V/K178R AGT genotype and lung cancer risk.

O6-pyridyloxobutylguanine adducts contribute to the mutagenic properties of pyridyloxobutylating agents.

The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are potent carcinogens in animal models and likely human carcinogens. Both NNK and NNN can be activated to a pyridyloxobutylating agent. This alkylating agent contributes to the carcinogenic effects of NNK and NNN via the formation of miscoding DNA adducts.

Development of a quantitative liquid chromatography/electrospray mass spectrometric assay for a mutagenic tobacco specific nitrosamine-derived DNA adduct, O6-[4-Oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine.

Liquid chromatography with electrospray tandem mass spectrometry (LC/ESI-MS/MS) was employed to quantify O6-[4-oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine (O6-pobdG), a mutagenic adduct formed by pyridyloxobutylating nitrosamines. Selected reaction monitoring (SRM) of the neutral loss of the sugar from protonated molecules of the adduct, [M + H - 116]+, was utilized for detection of O6-pobdG in pyridyloxobutylated DNA from both in vitro and in vivo sources. Quantitation was based on isotope dilution with synthetic O6-[1,2,2-2H3-4-oxo-4-(3-pyridyl)butyl]-2'-deoxyguanosine.

The repair of the tobacco specific nitrosamine derived adduct O6-[4-Oxo-4-(3-pyridyl)butyl]guanine by O6-alkylguanine-DNA alkyltransferase variants.

The tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent pulmonary carcinogen, both methylates and pyridyloxobutylates DNA. Both reaction pathways generate promutagenic O6-alkylguanine adducts. These adducts, O6-methylguanine (O6-mG) and O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-pobG), are repaired by O6-alkylguanine-DNA alkyltransferase (AGT).