Ovarian Susceptibility to Benzo[a]Pyrene: Tissue Burden of Metabolites and DNA Adducts in F-344 Rats

Ramesh, Aramandla; Archibong, Anthony E.; Niaz, Mohammad S.

doi:10.1080/15287394.2010.514225

Cited by 55 publications

(35 citation statements)

References 59 publications

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“…57 This method is effective and economical, but is limited to hydrophobic lesions such as those of polycyclic aromatic hydrocarbons and aromatic amines.…”

Section: Introductionmentioning

confidence: 99%

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

104

125

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Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations and potentially contributing to the development of cancer. Because of their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples, including immunoassay, HPLC, and 32P-postlabeling, isotope dilution high performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adduct concentrations in biological samples are between 0.01–10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry, especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS, have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke.

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“…57 This method is effective and economical, but is limited to hydrophobic lesions such as those of polycyclic aromatic hydrocarbons and aromatic amines.…”

Section: Introductionmentioning

confidence: 99%

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Tretyakova

Goggin

Sangaraju

et al. 2012

Chem. Res. Toxicol.

104

125

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“…It is unclear how these translate for the woman that smokes cigarettes while attempting to conceive; however, it is known that smoking leads to a reduction in ovarian reserve and an advancement of the age of menopause for the woman (167,301), potentially due to the influence of polycyclic hydrocarbons which are activated into more toxic metabolites by the liver (49,271). Further human studies have demonstrated that oocytes derived from cigarette smoking women undergoing IVF treatment have a greater number of immature oocytes (385), an increased thickness of the zona pellucida (310), with follicles containing higher level of markers of oxidative stress within the follicular fluid (252), and within the cumulus (316).…”

Section: Ovarian Functionmentioning

confidence: 99%

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Hart

2016

Physiological Reviews

168

119

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Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.

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“…Additionally, the preponderance of BaP-7,8-dihydro-diol in these samples is interesting, given the fact that this precursor of BPDE has been linked to BaP-induced cancer 38 and infertility. 13 …”

Section: Discussionmentioning

confidence: 99%

“…BaP metabolites were extracted twice with ethyl acetate and the extracts were analyzed by reverse phase HPLC for BaP metabolites as described previously. 13 Metabolite standards were obtained from the National Cancer Institute Chemical Carcinogen Repository (Midwest Research Institute, Kansas City, Missouri, USA).…”

Section: Methodsmentioning

confidence: 99%

Metabolism of the environmental toxicant benzo(a)pyrene by subcellular fractions of human ovary

et al. 2013

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Knowledge of the ability of the female reproductive system to metabolize environmental chemicals is critical not only from the standpoint of toxicity but also from infertility risk assessment. Benzo( a)pyrene (BaP) is a toxicant that is released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, BaP becomes activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. Studies on animal models conducted in our laboratories and those of others have shown that BaP possess endocrine disrupting properties. Thus, this chemical has the potential to cause infertility and cancers in the female genital tract. An understanding of BaP metabolism in the female reproductive system will be of importance in the diagnosis and management of female fertility as well as cancers in the reproductive tissues. Therefore, the objective of our study was to examine the metabolism of BaP by human ovarian subcellular fractions. Human ovary samples (eight individuals) were obtained from postoperative tissue removed from subjects with uterine tumors. Subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were prepared by differential centrifugation. BaP (1 μM and 3 μM) was individually incubated with individual subcellular fractions for 15 min and the products were analyzed by high-performance liquid chromatography. Among the different fractions tested, microsomal BaP metabolism was higher than the rest of the fractions. The BaP metabolites identified were as follows: BaP-9,10-diol, BaP-4,5-diol, BaP-7,8-diol, 9(OH) BaP, 3(OH) BaP, BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. Of interest was the presence of DNA-reactive metabolites such as BaP-3,6-dione, BaP-6,12-dione, and BaP 7,8-diol, which have been implicated in the causation of infertility and cancer. Our results indicate that women who are exposed to BaP via cigarette smoke, occupational settings, and diet are more likely at a larger risk of this toxicant-induced infertility and cancer than others.

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Ovarian Susceptibility to Benzo[a]Pyrene: Tissue Burden of Metabolites and DNA Adducts in F-344 Rats

Cited by 55 publications

References 59 publications

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Quantitation of DNA Adducts by Stable Isotope Dilution Mass Spectrometry

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Metabolism of the environmental toxicant benzo(a)pyrene by subcellular fractions of human ovary

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