Abstract:
:Propylene oxide, a widely used monofunctional alkylating agent, has been shown to be genotoxic in in vitro test systems and induces tumors in the nasal tissues of experimental animals. Propylene oxide, like related alkylating agents, forms several different adducts with DNA bases, but predominantly at the 7-position of guanine. We have previously described the in vitro and in vivo formation and stability of this major adduct. The aim of the present study was to perform a similar investigation of other adducts of propylene oxide. 1-(2-Hydroxypropyl)adenine (1-HP-adenine) and 3-(2-hydroxypropyl)cytosine (3-HP-cytosine), as well as their rearrangement products to N(6)-(2-hydroxypropyl)adenine (N(6)-HP-adenine) and 3-(2-hydroxypropyl)uracil (3-HP-uracil), respectively, were analysed by a very sensitive (32)P-postlabelling method involving nuclease P1 enhancement and radioisotope detector-coupled HPLC separation. All four adducts could be detected in DNA treated in vitro with propylene oxide. The sum of the levels of 1- and N(6)-HP-adenine amounted to 3.5% and the sum of 3-HP-cytosine and 3-HP-uracil to 1.7%, respectively, of 7-(2-hydroxypropyl)guanine (7-HP-guanine). In male Fischer 344 rats exposed to 500 p.p.m. propylene oxide by inhalation for 20 days, 1-HP-adenine was detected in all analysed tissues, including nasal epithelium, lung and lymphocytes, whereas N(6)-HP-adenine was only found in the tissues of the nasal cavities. The highest level of 1-HP-adenine (2.0 mol/10(6) mol of normal nucleotides, i.e. 2% of 7-HP-guanine) was found in the respiratory nasal epithelium, which also represents the major target for tumour induction in the rat following inhalation of propylene oxide. The levels of this adduct in the lung and in the lymphocytes were considerably lower, amounting to 15 and 9%, respectively, of that of the respiratory nasal epithelium. In rats killed 3 days after cessation of exposure, practically no decrease in 1-HP-adenine was observed, indicating no or very slow repair. 3-HP-uracil could only be detected in the respiratory nasal epithelia of propylene-exposed rats and its concentration was as low as 0.02 mol/10(6) mol of normal nucleotides (0.02% of 7-HP-guanine). Since 3-HP-uracil was chemically much more stable than the latter, the obtained animal data suggest repair of the cytosine and/or uracil adducts. Incubation of propylene oxide-reacted DNA with a protein extract from mammalian cells indicated that an enzymatic repair mechanism exists for removal of 3-HP-cytosine, but not for 3-HP-uracil or 1- and N(6)-HP-adenine. Another finding was that uracil glycosylase is probably not involved. The level of 1-HP-adenine in the propylene oxide-exposed rats was approximately 50 times lower than that of 7-HP-guanine. Nevertheless, this adduct is conveniently analysed and has high chemical stability and recovery, which results in high sensitivity (detection limit 0.3 mol/10(9) mol of normal nucleotides using 10 microgram DNA). 1-HP-adenine might, therefore, be considered as an alternative to 7-HP-guanine for monitoring exposure to propylene oxide.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Plna K,Nilsson R,Koskinen M,Segerbäck Ddoi
10.1093/carcin/20.10.2025keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
2025-32issue
10eissn
0143-3334issn
1460-2180journal_volume
20pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Modulation of microsome mediated benzo[a]pyrene (BP) metabolism by oleic and linoleic acids was studied. Oleic and linoleic acids did not influence the apparent activity of aryl hydrocarbon hydroxylase or the relative ratios of BP-7,8-dihydrodiol to phenol metabolites on high performance liquid chromatography. The tot...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.10.1253
更新日期:1983-10-01 00:00:00
abstract::We have recently shown that the prostaglandin E(2) (PGE(2)) receptor EP(3) plays an important role in suppression of colon cancer cell proliferation and that its deficiency enhances late stage colon carcinogenesis. Here we examined the effects of EP(3)-deficiency on two-stage skin carcinogenesis. 7,12-Dimethylbenz[a]a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi193
更新日期:2005-12-01 00:00:00
abstract::Four groups of six male Wistar rats (85 +/- 7 g) were fed a diet containing 0% (control) or 2% of the carcinogenic food antioxidant butylated hydroxyanisole (BHA) for 2 weeks. In this experiment, feeding 2% BHA is equivalent to a dose of 2.1 +/- 0.3 g BHA/kg/day. One 0% BHA and one 2% BHA-fed group of rats were daily ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.10.1947
更新日期:1989-10-01 00:00:00
abstract::To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) mice...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs265
更新日期:2012-12-01 00:00:00
abstract::Both dehydroepiandrosterone (DHEA) and the synthetic steroid 16 alpha-Br-epiandrosterone (Br-Epi), a more potent inhibitor of glucose-6-phosphate dehydrogenase (G6PDH) than DHEA, inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of superoxide anion (O2-) formation by human neutrophils. DHEA has previo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.3.333
更新日期:1985-03-01 00:00:00
abstract::The transcription factor Sp1 has been implicated in cell-type-specific activation of transforming growth factor-beta (TGFbeta) target genes in normal epithelial cells as well as in aberrant gene activation by TGFbeta in epithelial tumor cells. Here, we have examined the interaction of Sp1 with components of the Smad s...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl078
更新日期:2006-12-01 00:00:00
abstract::Despite decreases in the cancer death rates in high-resource countries, such as the USA, the number of cancer cases and deaths is projected to more than double worldwide over the next 20-40 years. Cancer is now the third leading cause of death, with >12 million new cases and 7.6 million cancer deaths estimated to have...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp263
更新日期:2010-01-01 00:00:00
abstract::The activation of 2-nitrofluorene (2-NF) to reactive intermediates that bind covalently to DNA, RNA and protein has been investigated both in vitro and in the rat in vivo. In vitro, such binding was catalyzed by the hepatic microsomal fraction, was NADPH dependent and could be inhibited by SKF 525A, an inhibitor of cy...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.1.27
更新日期:1990-01-01 00:00:00
abstract::3-Methyladenine DNA glycosylases initiate base excision repair by flipping the nucleotide bearing the target base out of double-stranded DNA into an active site pocket for glycosylic bond cleavage and base release. Substrate bases for the murine 3-methyladenine DNA glycosylase (other than 3-methyladenine) include hypo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.5.901
更新日期:2000-05-01 00:00:00
abstract::Autoradiography has been used to study the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), 4-O-methyl TPA, and phorbol on metabolic cooperation between human diploid fibroblasts. When the donors, hypoxanthine-guanine phosphoribosyl transferase+ (HGPRT+) cells, and recipients, HGPRT- cells, were plated together i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.10.1207
更新日期:1982-01-01 00:00:00
abstract::Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.9.1817
更新日期:1997-09-01 00:00:00
abstract::Covalent binding to haemoglobin, plasma proteins and DNA was determined after intraperitoneal administration of radiolabelled diethylnitrosamine to mice. The level of alkylation of DNA in liver--the main site of activation--was found to be about two orders of magnitude higher than the level of alkylation of haemoglobi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.11.1915
更新日期:1988-11-01 00:00:00
abstract::Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation that promotes carcinogenesis in mice (intrinsic inflammation). The finding that patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, have an increased risk of lung cancer after...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp229
更新日期:2009-11-01 00:00:00
abstract::Tamoxifen is a non-steroidal anti-estrogen used for the treatment of breast cancer and, more recently, as a chemopreventive agent in healthy women at high risk of developing breast cancer. On the other hand, tamoxifen is a potent hepatocarcinogen in rats, with both tumor-initiating and tumor-promoting properties. Ther...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl050
更新日期:2006-08-01 00:00:00
abstract::The lymphocyte response to u.v. radiation (254 nm) was investigated by two different methods in 29 unselected patients with multiple epidermal cancer. The u.v.-induced DNA synthesis was determined as the increase in incorporation of [3H]thymidine in irradiated cells compared with nonirradiated cells after incubation f...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.6.843
更新日期:1985-06-01 00:00:00
abstract::3,3-[3H]Dimethyl-1-phenyltriazene, 1-(4-chlorophenyl)-3,3-[3H]dimethyltriazene and 3,3-[3H]dimethyl-1-(2,4,6-trichlorophenyl)-triazene methylate initiator tRNA in vitro only after pre-incubation with microsomal enzymes and NADPH. The finding confirms that procarcinogenic dialkyl aryltriazenes must be enzymatically con...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.7.995
更新日期:1985-07-01 00:00:00
abstract::A 25mer oligonucleotide containing a single N-(deoxyguanosin-8-yl-)-1-aminopyrene (dGAP), the major DNA adduct formed by reductively activated 1-nitropyrene, was synthesized. The adduct was located at nucleotide 21 from the 3' end. DNA synthesis on this template by human DNA polymerases alpha and beta, HIV reverse tra...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.4.811
更新日期:1995-04-01 00:00:00
abstract::Common genetic variation may play an important role in altering lung cancer risk. We conducted a pathway-based candidate gene evaluation to identify genetic variations that may be associated with lung cancer in a population-based case-control study in Xuan Wei, China (122 cases and 111 controls). A total of 1260 singl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn178
更新日期:2008-10-01 00:00:00
abstract::The haloethylnitrosoureas form a cytotoxic DNA cross-link in a series of reactions which involves initial alkylation of the O6 position of guanine and rearrangement to the intermediate, 1,O6-ethanoguanine; 1,O6-ethanoguanine then reacts with a neighboring cytosine base. O6-Alkylguanine-DNA alkyltransferase can interru...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.2.195
更新日期:1993-02-01 00:00:00
abstract::The nature of mutagenic burden due to occupational exposure to tobacco flakes and dust was determined among 20 female tobacco processors (TP) and 20 matched controls (C) by testing urinary mutagenicity in the Ames assay. In addition, urinary cotinine was estimated as a marker of tobacco absorption. Workers and control...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.5.1095
更新日期:1995-05-01 00:00:00
abstract::Expression of blood group-related antigens (BGRAs) A, B, H, Le(b), Le(x) and Le(y) was examined immunohistochemically in neoplastic and hyperplastic lesions induced by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters to determine a relationship between histological and biological patterns of the lesion and expression...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.3.441
更新日期:1991-03-01 00:00:00
abstract::Nitric oxide (NO) is a short-lived, pleiotropic molecule that affects numerous critical functions in the body. Presently, there are markedly conflicting findings in the literature regarding NO and its role in carcinogenesis and tumor progression. NO has been shown to have dichotomous effects on cellular proliferation,...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgt034
更新日期:2013-03-01 00:00:00
abstract::Low selenium (Se) status correlates with increased risk of colorectal cancer (CRC). Since Se exerts its biological roles through the selenoproteins, genetic variations in selenoprotein genes may influence susceptibility to CRC. This study analysed 12 single-nucleotide polymorphisms (SNPs) in selenoprotein genes [gluta...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq076
更新日期:2010-06-01 00:00:00
abstract::Metastatic disease is the leading cause of cancer mortality. Identifying biomarkers and regulatory mechanisms is important toward developing diagnostic and therapeutic tools against metastatic cancer. In this study, we demonstrated that podocalyxin-like 1 (PODXL) is overexpressed in breast tumor cells and increased in...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgu139
更新日期:2014-11-01 00:00:00
abstract::Lung cancer is the leading cause of cancer-related mortality, with most cases attributed to tobacco smoking, in which nicotine-derived nitrosamine ketone (NNK) is the most potent lung carcinogen. The ADAM17 protease is responsible for the ectodomain shedding of many pro-tumorigenic cytokines, growth factors and recept...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz123
更新日期:2020-06-17 00:00:00
abstract::Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxifica...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi359
更新日期:2006-08-01 00:00:00
abstract::We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by ind...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp315
更新日期:2010-03-01 00:00:00
abstract::The purpose of this study was to determine if decreasing dietary protein from 24% (high protein) to 5% casein (low protein), substituting sucrose and cornstarch isocalorifically for casein, would modify the activity of protein kinase C (PKC) alpha and beta isoenzymes, as well as the expression of PKC alpha, beta, delt...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.5.1233
更新日期:1995-05-01 00:00:00
abstract::Alternative pre-messenger RNA (mRNA) splicing is a key molecular event that allows for protein diversity and plays important roles in development and disease. Alternative pre-mRNA splicing regulations during spermatogenesis and alternative pre-mRNA splicing etiology in testicular tumorigenesis are yet to be characteri...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm194
更新日期:2007-12-01 00:00:00
abstract::The activity of nuclear transcription factors is often regulated by specific kinase-signaling pathways. We have previously shown that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) stimulates activator protein-1 activity through the p38 mitogen-activated protein kinase (MAPK). Here, we show that DD...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn213
更新日期:2009-01-01 00:00:00