Cervical biopsy samples were taken from 40 women, aged between 31 and 72, undergoing hysterectomies. Twenty-two of the women were smokers, four were ex-smokers and 14 were non-smokers. DNA was isolated and analysed using 32P-postlabelling, after butanol extraction or nuclease P1 digestion enhancement of the adducts. Resolution of the adducts was by thin-layer chromatography on polyethyleneimine (PEI)-cellulose. The pattern of adducts seen was similar to smoking-related adducts detected in other tissues and consisted mainly of a diagonal zone of radioactivity. With the butanol extraction enrichment method, the levels of adducts in DNA from the 22 smokers ranged from 1.65 to 6.04 adducts/10(8) nucleotides (mean = 3.70, SD = 1.36), in DNA from non-smokers from 1.16 to 3.98 (mean = 2.04, SD = 0.77) and in samples from ex-smokers from 2.57 to 3.35 (mean = 2.86, SD = 0.37). The increase in adduct levels in smokers compared with non-smokers was highly significant (Mann-Whitney test p = 0.0005, two-tailed). When analysed by the nuclease P1 digestion enhancement method, total adduct levels in samples from smokers (mean = 2.95, SD = 1.77) were not significantly different (p = 0.3, two-tailed) from levels in non-smokers (mean = 2.34, SD = 0.96). However, the level of a minor discrete adduct spot was significantly lower (p = 0.02, two-tailed) in smokers (mean = 0.19, SD = 0.36) than in non-smokers (mean = 0.39, SD = 0.41). The results indicate that some of the DNA adducts detected in cervical epithelium correlate with tobacco smoking and support the hypothesis that smoking-related cervical cancer results from exposure to genotoxic components of cigarette smoke that become activated to DNA-binding products in this tissue.
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http://dx.doi.org/10.1016/0165-1161(94)90057-4 | DOI Listing |
Eur J Med Chem
January 2025
University of Pisa, Department of Chemistry and Industrial Chemistry, Via G. Moruzzi 13, I-56124, Pisa, Italy. Electronic address:
The novel diiron amine complexes [FeCp(CO)(NHR')(μ-CO){μ-CN(Me)(Cy)}]CFSO [R' = H, 3; Cy, 4; CHCHNH, 5; CHCHNMe, 6; CHCH(4-CHOMe), 7; CHCH(4-CHOH), 8; Cp = η-CH, Cy = CH = cyclohexyl] were synthesized in 49-92 % yields from [FeCp(CO)(μ-CO){μ-CN(Me)(Cy)}]CFSO, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [FeCp(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CFSO (R = Cy, 2a; Me, 2b; Xyl = 2,6-CHMe, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia.
The apurinic/apyrimidinic site (AP site) is a highly mutagenic and cytotoxic DNA lesion. Normally, AP sites are removed from DNA by base excision repair (BER). Methoxyamine (MOX), a BER inhibitor currently under clinical trials as a tumor sensitizer, forms adducts with AP sites (AP-MOX) resistant to the key BER enzyme, AP endonuclease.
View Article and Find Full Text PDFJ Biol Inorg Chem
January 2025
Department of Chemistry, Wayne State University, Detroit, MI, USA.
The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2# Xuelin Road, Nanjing 210023, People's Republic of China.
Acrolein (ACR) present in vivo and in vitro can damage proteins and DNA, linking it to various chronic diseases. In this paper, ergothioneine (EGT), abundant in edible mushrooms, has been studied for its ability to trap ACR and its reaction pathway with ACR at high temperatures using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). We synthesized the adducts (EGT-ACR-1 and EGT-ACR-2), elucidating their structure and reaction site through HRMS and nuclear magnetic resonance.
View Article and Find Full Text PDFDev Cogn Neurosci
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Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, United States; The Child Mind Institute, New York, NY, United States. Electronic address:
Reading difficulties and exposure to air pollution are both disproportionately high among youth living in economically disadvantaged contexts. Critically, variance in reading skills in youth living in higher socioeconomic status (SES) contexts largely derives from genetic factors, whereas environmental factors explain more of the variance in reading skills among youth living in lower SES contexts. Although reading research has focused closely on the psychosocial environment, little focus has been paid to the effects of the chemical environment.
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