ライフサイエンスコーパス: BPDE

1 BPDE adduct stereochemistry influenced incision activity

2 BPDE treatment induced the re-localization of an ectopic

3 BPDE was also unable to induce COX-2 expression after RA

4 BPDE-DNA adduct levels were determined by the (32)P-post

5 BPDE-induced 3p21.3 aberrations were associated with an

6 BPDE-induced 3p21.3 aberrations were scored by fluoresce

7 BPDE-induced formation of green fluorescent protein-polk

8 BPDE-induced guanine adducts were produced nonrandomly a

9 f BPDE-N(2)-dG on-column, corresponding to 1 BPDE-N(2)-dG adduct per 10(11) nucleotides (1 adduct per

10 vectors containing single 10S-BPDE-dG or 10R-BPDE-dG adducts positioned at G(0) or G(-1) in the analy

11 Four vectors containing single 10S-BPDE-dG or 10R-BPDE-dG adducts positioned at G(0) or G(-

12 may enhance overall mutagenicity of the 10S-BPDE-dG lesion and contribute to the much higher carcino

13 n synthesis past dG-(+)- or dG-(-)-anti-N(2)-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrob

14 (+)-trans-dG-N(2)-BPDE and (-)-trans-dG-N(2)-BPDE adduction to be 26.5% and 17.5%, respectively.

15 is efficiently inserted opposite all dG-N(2)-BPDE adducts and extended past these lesions.

16 ed in mutagenic events attributed to dG-N(2)-BPDE adducts in human cells.

17 requencies associated with (+)-trans-dG-N(2)-BPDE and (-)-trans-dG-N(2)-BPDE adduction to be 26.5% an

18 mutational frequencies of (+)-trans-dG-N(2)-BPDE and (-)-trans-dG-N(2)-BPDE were reduced to 11.1% an

19 ing properties were similar to other dG-N(2)-BPDE isomers.

20 s containing a single stereoisomeric dG-N(2)-BPDE lesion were used as DNA templates for primer extens

21 n was retarded one base prior to the dG-N(2)-BPDE lesion; when incubated for longer times or with hig

22 se, opposite all four stereoisomeric dG-N(2)-BPDE lesions.

23 on synthesis (F(ins) x F(ext)) of dC.dG-N(2)-BPDE pairs was 2-6 orders of magnitude higher than that

24 Although (+)-cis-dG-N(2)-BPDE was most effective in blocking translesion synthesi

25 When the cytosine 5' to dG-N(2)-BPDE was replaced by 5-methylcytosine, the mutational fr

26 TGT) modified with (+)- or (-)-trans-dG-N(2)-BPDE were incorporated into single-stranded shuttle vect

27 (+)-trans-dG-N(2)-BPDE and (-)-trans-dG-N(2)-BPDE were reduced to 11.1% and 10.6%, respectively, whil

28 (+)-trans-dG-N(2)-BPDE, a major BPDE-DNA adduct, promoted small amounts of

29 he modified DNA to 2'-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-label

30 s-derived DNA sequence, the majority of N(2)-BPDE-dG adducts originated from the first position of th

31 odify the diastereomeric composition of N(2)-BPDE-dG adducts.

32 PLC-ESI-MS/MS peak area ratios of (15)N-N(2)-BPDE-dG and N(2)-BPDE-dG.

33 cer, suggesting that factors other than N(2)-BPDE-dG formation are responsible for these mutations.

34 On the contrary, the pattern of N(2)-BPDE-dG formation within the p53 exon 5 sequences did no

35 ectrometry analysis (HPLC-ESI-MS/MS) of N(2)-BPDE-dG lesions.

36 ormed a direct quantitative analysis of N(2)-BPDE-dG originating from specific guanine nucleobases wi

37 N(2)-BPDE-dG yield was enhanced by the presence of 5-Me subst

38 yl)-7,8,9,10-tetra hydrobenzo[a]pyrene (N(2)-BPDE-dG).

39 k area ratios of (15)N-N(2)-BPDE-dG and N(2)-BPDE-dG.

40 erentially the correct base opposite dG-N(2)-BPDE.

41 ker and nonsmoker DNA containing 3.1 and 1.3 BPDE-N(2)-dG adducts per 10(11) nucleotides, respectivel

42 et, there has been no crystal structure of a BPDE DNA adduct.

43 We report here the crystal structure of a BPDE-adenine adduct base-paired with thymine at a templa

44 Finally, although mutagenic TLS across BPDE-dG largely depends on RAD18, experiments using Polk

45 l to mutagenic, but not accurate, TLS across BPDE-dG.

46 yrene dihydrodiol epoxide-derived dG adduct (BPDE-dG) using a plasmid bearing a single BPDE-dG and ge

47 iol epoxide-induced damage, and repair after BPDE-induced damage were all significantly higher in cas

48 deficient cells show reduced viability after BPDE challenge compared with wild-type cells (but surviv

49 neal injection were 420-430 and 600-830 amol BPDE-type adducts per microg DNA.

50 induction of mutations by BPDE, we analyzed BPDE mutagenesis in three CpG methylated target genes: a

51 resent the excision repair maps for CPDs and BPDE-dG adducts generated by tXR-Seq for the human genom

52 With both B[a]P-7,8-dihydrodiol and BPDE-2 treatment, changes in anti- and pro-apoptotic eve

53 d are influenced by cytosine methylation and BPDE stereochemical considerations.

54 f interest because the (+)-7R,8S,9S,10R-anti-BPDE enantiomer is highly tumorigenic in rodents, while

55 in rodents, while the (-)-7S,8R,9R,10S-anti-BPDE enantiomer is not.

56 Both (+)- and (-)-anti-BPDE bind covalently with DNA predominantly by trans add

57 cancer cells by the ultimate carcinogen anti-BPDE accelerates the further development of lung carcino

58 tioselectivity for the carcinogenic (+)-anti-BPDE over (-)-anti-BPDE.

59 , C12-Viologen) were employed to detect anti-BPDE damage to DNA.

60 ene-r-7,t-8-dihydrodiol-t-9,10-epoxide (anti-BPDE) is a known carcinogen that damages DNA, and this d

61 zo(a)pyrene (BP)-7,8-diol-9,10-epoxide (anti-BPDE) resulted in a concentration- and time-dependent in

62 [a]pyrene-7,8-dihydrodiol-9,10-epoxide (anti-BPDE).

63 nzo[a]pyrene-7,8-diol-9,10-epoxide [(+)-anti-BPDE] is more than 5-fold higher for hGSTA1-1 than for h

64 yrene-7,8-dihydrodiol-9,10-epoxide, (+)-anti-BPDE, which reacts via its 10-position with N2-dG in DNA

65 30 mutant cells lacking Pol(eta), (+/-)-anti-BPDE-induced mutagenesis was reduced and accompanied by

66 in the presence of DNA damage following anti-BPDE exposure, whereas control cells resumed only after

67 ncrease in catalytic efficiency for (+)-anti-BPDE-GSH conjugation.

68 a DNA covalent adduct derived from (+)-anti-BPDE [(+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,

69 ic hydrocarbon-DNA adducts derived from anti-BPDE.

70 oles of Pol(zeta) and Pol(eta) in (+/-)-anti-BPDE-induced mutagenesis.

71 de that Cdc25B has an essential role in anti-BPDE-induced neoplastic transformation, including regula

72 d Cdk1 phosphorylation were observed in anti-BPDE-treated cells.

73 benzo[a]pyrene diol epoxide isomer [(+)-anti-BPDE] to N(2)-guanine (G*).

74 s after chronic exposure to 0.1 micro M anti-BPDE.

75 cells proficient in mutagenesis, (+/-)-anti-BPDE induced 85% base substitutions with predominant G -

76 of mGSTA1-1 for GSH conjugation of (+)-anti-BPDE is >3-fold higher as compared with mGSTA2-2.

77 primary product of the reaction of (+)-anti-BPDE with DNA, the (+)-trans-anti-benzo[a]pyrene diol ep

78 cient enzyme for GSH conjugation of (-)-anti-BPDE.

79 the efficient global genomic repair of anti-BPDE-induced DNA adducts from the overall genome, but no

80 the carcinogenic (+)-anti-BPDE over (-)-anti-BPDE.

81 mic (+/-)- or enantiomerically pure (+)-anti-BPDE solutions followed by electrochemical interrogation

82 poxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) causes a marked increase in the expression of Cdc2

83 ,8,9,10-tetrahydrobenzo[a]pyrene [(+/-)-anti-BPDE] to double-stranded (ds) 5'-PO4--ACCCGCGTCCGCGC-3'/

84 7,8,9,10-tetrahydrobenzo[a]pyrene, [(+)-anti-BPDE].

85 -(5'-...TTTA(2)TA...) were synthesized (anti-BPDE-N(6)-dA denotes an adduct formed from the reaction

86 ectrochemical responses showed that (+)-anti-BPDE primarily adopts a minor groove bound orientation w

87 These results show that (+/-)-anti-BPDE-induced mutagenesis in yeast requires Pol(zeta) and

88 posure of wild-type (Cdc25B+/+) MEFs to anti-BPDE (0.1 micromol/L) caused neoplastic transformation c

89 Similar to (+)-anti-BPDE, however, the SIFS mutant was the most efficient en

90 the Cdc25B null MEFs were resistant to anti-BPDE-induced transformation.

91 A1-1, mGSTA4-4, and hGSTP1-1 toward (+)-anti-BPDE.

92 lytic efficiency of hGSTA2-2 toward (-)-anti-BPDE was increased to a level close to that of hGSTA1-1

93 cells of a site-specific 10S (+)-trans-anti-BPDE-N(2)-dG adduct and the stereoisomeric 10R (-)-trans

94 n synthesis opposite (+)- and (-)-trans-anti-BPDE-N(2)-dG DNA adducts with predominant G incorporatio

95 ic 10S (+)-trans-anti- or 10R (-)-trans-anti-BPDE-N(6)-dA residues at A(1) or A(2) within the TATA se

96 ct and the stereoisomeric 10R (-)-trans-anti-BPDE-N2-dG adduct.

97 d mutagenesis of the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts, Poleta, Polzeta and Rev1 togethe

98 -dG in DNA to form the adduct (+)-trans-anti-BPDE-N2-dG.

99 and 4% G insertions opposite (-)-trans-anti-BPDE-N2-dG.

100 and 7% G insertions opposite (+)-trans-anti-BPDE-N2-dG; and 89% C, 4% A and 4% G insertions opposite

101 ions are attributed mainly to (+)-trans-anti-BPDE-N2dG and the intercalated conformations to (+)-cis-

102 ely -0.38 V and -0.55 V vs Ag/AgCl upon anti-BPDE exposure.

103 tosine methylation on the reaction with anti-BPDE at a known hotspot DNA damage site was studied elec

104 3 mutant cells lacking Pol(zeta), (+/-)-anti-BPDE-induced mutagenesis was mostly abolished, leading t

105 a) and UvrABC(Tma) specifically incised both BPDE-adducted plasmid DNAs and site-specifically modifie

106 results suggest that the hydrophobic, bulky BPDE residues influence the binding of TBP by mechanisms

107 ined UvrB recognition of both "normal" bulky BPDE-DNA and protein-cross-linked DNA (DPC) adducts and

108 This was in contrast to p38 activation by BPDE-2, an event that was independent of Ah receptor fun

109 ficantly, we find that stimulation of ATR by BPDE-damaged DNA exhibits strong dependence on the lengt

110 mours of smokers are predominantly caused by BPDE.

111 ral lymphocytes after in vitro challenged by BPDE.

112 s demonstrate that the activation of DDX3 by BPDE, can promote growth, proliferation and neoplastic t

113 ed to the complementary strands, followed by BPDE treatment and liquid chromatography-electrospray io

114 We hypothesize that mutations induced by BPDE DNA adducts are mainly generated through an error-p

115 CpG methylation in induction of mutations by BPDE, we analyzed BPDE mutagenesis in three CpG methylat

116 ating cell nuclear antigen was unaffected by BPDE treatment.

117 In Rad18(-/-) cells, BPDE induces elevated and persistent activation of check

118 the complementary strand opposite a (+)-cis-BPDE-N(2)-dG lesion led to a significant reduction in bo

119 tion was similar with (+)-trans- and (+)-cis-BPDE-adducted substrates, suggesting that UvrAB binds bo

120 es containing a single (+)-trans- or (+)-cis-BPDE adduct.

121 omeric (+)- or (-)-trans- or (+)- or (-)-cis-BPDE-N(2)-dG lesions in DNA duplexes of known conformati

122 recipitation technique to identify and clone BPDE-binding DNA fragments.

123 nerated during replication of DNA containing BPDE adducts.

124 a)pyrene-7,8-dihydrodiol-9,10-epoxide (N6-dA-BPDE), and N4-deoxycytidine-benzo(a)pyrene-7,8-dihydrodi

125 The concentrations of N2-dG-BPDE, N6-dA-BPDE, and N4-dC-BPDE adducts were determined to be 1.17,

126 rations of N2-dG-BPDE, N6-dA-BPDE, and N4-dC-BPDE adducts were determined to be 1.17, 0.97, and 0.68

127 a)pyrene-7,8-dihydrodiol-9,10-epoxide (N4-dC-BPDE) were identified.

128 (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotid

129 pture antibody in a sandwich ELISA to detect BPDE-HSA adducts directly in 1-mg samples of HSA or 20 m

130 a)pyrene-7,8-dihydrodiol-9,10-epoxide (N2-dG-BPDE); N6-deoxyadenosine-benzo(a)pyrene-7,8-dihydrodiol-

131 The concentrations of N2-dG-BPDE, N6-dA-BPDE, and N4-dC-BPDE adducts were determined

132 PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE).

133 Adducts of benzo[a]pyrene-diolepoxide (BPDE) with blood nucleophiles have been used as biomarke

134 onooxygenation that results in diolepoxides (BPDE) and one-electron oxidation that yields a BP radica

135 acked, and intercalated conformations of DNA-BPDE adducts formed in lung tissue.

136 Cr(VI) exposure also greatly enhanced BPDE-induced killing in NER-proficient cells.

137 low mutation frequency, it greatly enhanced BPDE-induced mutations in nucleotide excision repair (NE

138 benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), using methodology applicable to correlate gene da

139 benoz[a]pyrene-7,8-dihyrodiol-9,10-epoxide (BPDE)-adducted substrates.

140 rcinogen benzo[a]pyrene dihydrodiol epoxide (BPDE) induces a Chk1-dependent S-phase checkpoint.

141 ponse to benzo(a)pyrene dihydrodiol epoxide (BPDE), a genotoxin that causes bulky DNA adducts, Hus1-n

142 enotoxin benzo[a]pyrene dihydrodiol epoxide (BPDE).

143 rcinogen benzo[a]pyrene-dihydrodiol epoxide (BPDE).

144 bacco exposure (benzo[a]pyrene diol epoxide (BPDE) and bleomycin) to see whether sensitivity to these

145 (-)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA adduct at the second position of codon 273 of

146 Benzo[a]pyrene,diol epoxide (BPDE) is a potent cigarette smoke carcinogen that forms

147 itro induced by benzo[a]pyrene diol epoxide (BPDE) is an independent risk factor for SCCHN.

148 igenic (-)-anti-benzo[a]pyrene diol epoxide (BPDE) that react with DNA via trans epoxide opening to f

149 nine adducts of benzo[a]pyrene diol epoxide (BPDE) was noted in a bubble of six mismatched nucleotide

150 ced in vitro by benzo(a)pyrene diol epoxide (BPDE), a bioactivated form of benzo(a)pyrene.

151 Benzo(a)pyrene diol epoxide (BPDE), an active metabolite of the tobacco carcinogen be

152 ent carcinogen, benzo[a]pyrene diol epoxide (BPDE), constitute a strong signal for TopBP1-dependent A

153 Benzo[a]pyrene diol epoxide (BPDE), the active metabolite of benzo[a]pyrene present i

154 d in mammals to benzo[a]pyrene diol epoxide (BPDE), which forms covalent DNA adducts and induces tumo

155 ly activated to benzo[a]pyrene diol epoxide (BPDE), which then can react with DNA to form carcinogeni

156 l predictors of benzo[a]pyrene diol epoxide (BPDE)-induced adduct levels and their associations with

157 enic metabolite benzo[a]pyrene diol epoxide (BPDE).

158 igenic (+)-anti-benzo[a]pyrene diol epoxide (BPDE).

159 Benzo[a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke and environm

160 249, and 250 to benzo(a)pyrene-diol-epoxide (BPDE), an active metabolite of BP in human bronchial epi

161 ppaB (NFkappaB) induced by BaP diol-epoxide (BPDE), the ultimate carcinogen of BaP, in mouse epiderma

162 repair of anti-benzo-(a)pyrene-diol-epoxide (BPDE)-DNA adducts and related effects using human fibrob

163 bleomycin- and benzo[a]pyrene diol-epoxide (BPDE)-induced chromatid breaks (by mutagen-sensitivity a

164 s, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of G

165 C radiation, and benzo[a]pyrenediol epoxide (BPDE).

166 a]P-r-7,t-8-dihydrodiol-t-9,10-epoxide(+/-) (BPDE-2) were found to induce apoptosis in human HepG2 ce

167 ighly reactive benzo[a]pyrene diol epoxides (BPDE), which in turn can form chemically stereoisomeric

168 e enantiomeric benzo[a]pyrene diol epoxides (BPDEs), (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,

169 n the ability of the repair enzyme to excise BPDE-induced lesions, and thus the slowly repaired lesio

170 and 1.93 ng/mg HSA (1010, 220, and 28.9 fmol BPDE equiv/mg HSA)--were significantly different (P<0.05

171 Following BPDE treatment and hydrolysis of the modified DNA to 2'-

172 eomycin-induced chromosome breaks, .0036 for BPDE-induced chromosome breaks, and .0397 for BPDE-induc

173 PDE-induced chromosome breaks, and .0397 for BPDE-induced DNA damage, indicating that these higher-or

174 in quartiles were 2.34, 9.14, and 54.04 for BPDE sensitivity and 1.92, 3.33, and 7.15 for bleomycin

175 idence interval) for OPL risk were noted for BPDE sensitivity [12.96 (5.51, 30.46)] and bleomycin sen

176 nd 3' and eighth phosphodiester bond 5' from BPDE-modified guanosine.

177 different DNA environments, which arise from BPDE damage and are influenced by cytosine methylation a

178 ic fibroblasts (MEFs) failed to recover from BPDE-induced S-phase arrest, while exhibiting normal rec

179 transgenic mice show defective recovery from BPDE-induced S-phase checkpoints.

180 Furthermore, BPDE induced time-dependent methylation of RAR-beta(2) g

181 Furthermore, BPDE-DNA adduct structure and stereochemistry cannot be

182 Oligodeoxyribonucleotides ((5)(')GAGGTGCG(BPDE)TGTTTGT) modified with (+)- or (-)-trans-dG-N(2)-BP

183 igonucleotides and 1.5-fold greater on [(3)H]BPDE-adducted plasmid DNAs.

184 eleased from human DNA upon acid hydrolysis, BPDE-N(2)-dG adducts have rarely if ever been observed d

185 The persistent S-phase arrest in BPDE-treated Polk(-/-) cells was associated with increas

186 ng BPDE-HSA/mg HSA) detected differences in BPDE-HSA levels in the a priori expected directions.

187 5 in the chromatin fraction was inhibited in BPDE-treated cells.

188 ith the beta-globin origin of replication in BPDE-treated cells.

189 ion that MAP kinases play a critical role in BPDE-2-induced apoptosis was shown by inhibiting caspase

190 hk1-dependent inhibition of DNA synthesis in BPDE-treated cells occurred without detectable changes i

191 n contrast, fraction RU-F004 did not inhibit BPDE-induced AP-1 or NFkappaB activities in Cl 41 cells.

192 ase checkpoint signaling partially inhibited BPDE-induced PCNA ubiquitination and prevented interacti

193 wnregulation of the E3 ligase Rad18 inhibits BPDE-induced PCNA ubiquitination and association between

194 as detection antibody, that detected intact BPDE adducts in HSA isolated from plasma.

195 195, we modified the ELISA to measure intact BPDE-HSA directly in human plasma.

196 ms facilitate the formation of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientat

197 To gain molecular insights into BPDE-induced mutagenesis, we examined in vivo translesio

198 a nanocolumn, four positional isomeric (+/-)-BPDE-oligonucleotide adducts were separated and identifi

199 ly established concentration of 4 micromol/L BPDE to treat short-term cultured primary lymphocytes fo

200 actions of an electrophilic metabolite like BPDE-2 to the regulation of programmed cell death.

201 At low BPDE adduct levels (10-50 adducts/10(8) nucleotides), re

202 rors that are a consequence of detecting low BPDE-HSA concentrations in the general population.

203 (+)-trans-dG-N(2)-BPDE, a major BPDE-DNA adduct, promoted small amounts of dTMP, dAMP, a

204 We found that mean BPDE-DNA adduct levels (the relative adduct labeling x 1

205 We found that the mean BPDE-induced chromatid breaks per cell were higher in ca

206 postlabeling method was then used to measure BPDE-induced DNA adducts in the host cells.

207 , however, inhibited by the B[a]P metabolite BPDE through a p53-dependent pathway.

208 posed to doses of 0.125, 0.5, and 1.0 microM BPDE, showed G:C to T:A transversions at codon 157 at a

209 wo separate experiments with either 2 microM BPDE for 24 h or 0.03 units/ml bleomycin for 5 h, and th

210 In addition, there were significantly more BPDE-induced chromosome aberrations at the 3p21.3 locus

211 and nonsmoking subjects (range 0.280-2.88 ng BPDE-HSA/mg HSA) and from highway workers with and witho

212 re to asphalt emissions (range 0.346-13.9 ng BPDE-HSA/mg HSA) detected differences in BPDE-HSA levels

213 were shown to be resistant to the actions of BPDE-2-induced apoptosis as determined by annexin V anal

214 ys paired wells with and without addition of BPDE tetrols to deactivate 8E11.

215 had a limit of detection (LOD) of 1 amol of BPDE-N(2)-dG on-column, corresponding to 1 BPDE-N(2)-dG

216 we have investigated the molecular basis of BPDE-induced S-phase arrest.

217 The degree of BPDE sensitivity at 3p21.3 and risk for OPLs increased i

218 mass spectrometry (LC-MS)-based detection of BPDE-N(2)-dG in BaP-treated rodents, and indirectly thro

219 These doses of BPDE induced higher frequencies, ranging from 4-12-fold,

220 His) counteracted the detrimental effects of BPDE on BRCA-1 promoter activity and protein levels.

221 The inhibitory effects of BPDE on DNA synthesis, Cdc45/Mcm7 associations, and inte

222 To investigate the direct effects of BPDE on gene expression, we used our newly developed DNA

223 To evaluate the effects of BPDE on human breast epithelial cells, we exposed an imm

224 S-phase checkpoint, we tested the effects of BPDE on the chromatin association of DNA replication fac

225 , an event that can lead to the formation of BPDE-2.

226 cation of DNA, resulting in the formation of BPDE-N(2)-dG, an adduct formed between deoxyguanosine an

227 n and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls

228 The mean frequency of BPDE-induced chromatid breaks was significantly higher i

229 nzo[a]pyrene tetrols following hydrolysis of BPDE adducts from lymphocyte DNA or human serum albumin

230 fractions did not result in an inhibition of BPDE binding to DNA; thus, this was not a mechanism of r

231 RU-DM, or RU-ME resulted in an inhibition of BPDE-induced AP-1 and NFkappaB activities.

232 thylated CpGs correlated with high levels of BPDE adducts formed at such sites.

233 patients had significantly higher levels of BPDE-DNA adducts than did the controls (mean +/- SD per

234 The respective geometric mean levels of BPDE-HSA adducts--67.8, 14.7, and 1.93 ng/mg HSA (1010,

235 nalyses showed consistently higher levels of BPDE-induced adducts in cases than in controls, regardle

236 relationship between the quartile levels of BPDE-induced DNA adducts and the risk of lung cancer was

237 ELISA measurements of BPDE-HSA in plasma from smoking and nonsmoking subjects

238 lp us to better understand the mechanisms of BPDE-induced carcinogenesis.

239 fter 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evalu

240 We performed molecular modelling of BPDE-adducted TP53 duplex sequences to determine the deg

241 wn that the cytotoxicity and mutagenicity of BPDE are mainly caused by the formation of DNA adduct, w

242 y and smoking were significant predictors of BPDE-DNA adduct levels in controls.

243 Potential predictors of BPDE-DNA adducts were evaluated by stratification and mu

244 flect either sequence-specific reactivity of BPDE and/or inefficient repair of BPDE-DNA adducts posit

245 R) to demonstrate an increased reactivity of BPDE toward guanine nucleobases within codons 157, 248,

246 ctivation assay, we found that the repair of BPDE-DNA adduct in a luciferase reporter gene is greatly

247 on, it significantly inhibited the repair of BPDE-DNA adducts from genomic DNA in NER-proficient cell

248 ctivity of BPDE and/or inefficient repair of BPDE-DNA adducts positioned at this site.

249 ition, we report the sequence specificity of BPDE-dG excision repair using tXR-seq.

250 ated whether 3p21.3 is a molecular target of BPDE damage in lymphocytes of patients with OPLs.

251 hermore, 3p21.3 may be a molecular target of BPDE in OPLs.

252 gher carcinogenicity and mutagenicity of (+)-BPDE-2 compared with its (-)-enantiomer.

253 ca) with 4-fold greater incision activity on BPDE-adducted oligonucleotides and 1.5-fold greater on [

254 The inhibitory effects of RU-ME on BPDE-induced activation of AP-1 and NFkappaB appear to b

255 lymerase(s) can insert a nucleotide opposite BPDE-dG, but the subsequent extension from miscoding ter

256 merase(s) could insert a nucleotide opposite BPDE-dG.

257 Similarly, treatment with B[a]P, TCDD, or BPDE failed to repress transcription from the pGL3-BRCA-

258 of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack

259 -9,10-epoxide derivatives of benzo[a]pyrene (BPDE) are of interest because the (+)-7R,8S,9S,10R-anti-

260 ,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) is strongly implicated as a cause of human lung ca

261 ,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) repressed BRCA-1 promoter activity and protein, wh

262 ,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), and DNA, producing promutagenic lesions, e.g., (+

263 ha-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene (BPDE).

264 ha-epoxy-7,8,9,10-tetrahydro benzo[a]pyrene (BPDE, an active metabolite of PAHs) induced cytotoxicity

265 t (BPDE-dG) using a plasmid bearing a single BPDE-dG and genetically engineered mouse embryonic fibro

266 ch was employed to insert the stereoisomeric BPDE residues into the known TATA box-TBP structure to r

267 After confirming that BPDE binds to HSA at His146 and Lys195, we modified the

268 These data further demonstrate that BPDE-induced gene alterations are important events in ca

269 This study demonstrated that BPDE-suppressed expression of RAR-beta(2) results in COX

270 We found that BPDE-induced COX-2 expression was through inhibition of

271 We show that BPDE adducted codon 157 has greater structural distortio

272 tion, while previous experiments showed that BPDE adducts cause T7RNAP to produce a ladder of truncat

273 The overall affinity of TBP for the BPDE-modified target DNA sequences was weakly enhanced i

274 ically required for normal recovery from the BPDE-induced S-phase checkpoint.

275 s DNA polymerases polkappa and poleta in the BPDE-induced S-phase checkpoint.

276 spectra and molecular modeling increase the BPDE binding constant to G in codon 248 consistent with

277 Two conformations of the BPDE, one intercalated between base pairs and another so

278 In the lacI gene, 68% (75 of 111) of the BPDE-induced mutations were G-to-T events, and 58 of 75

279 pG sequences in vivo, 83 of 147 (56%) of the BPDE-induced mutations were G-to-T transversions, and 58

280 may have a suboptimal ability to remove the BPDE-DNA adducts and so are susceptible to tobacco carci

281 at the eighth phosphodiester bond 5' to the BPDE-modified guanosine.

282 not rate-limiting for DNA synthesis when the BPDE-induced S-phase checkpoint was active.

283 rtalized human breast cell line, MCF 10A, to BPDE and characterized the gene expression pattern.

284 o not express RAR-beta(2) did not respond to BPDE for induction of COX-2.

285 owed a normal S-phase checkpoint response to BPDE (but failed to recover from the UV light-induced S-

286 e mutagenic DNA damage tolerance response to BPDE and support the development of strategies to target

287 d inhibition of DNA synthesis in response to BPDE did not require NBS1, a component of the IR-respons

288 ame cells) that was unchanged in response to BPDE.

289 cer suggests that subjects very sensitive to BPDE-induced DNA damage may have a suboptimal ability to

290 These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to t

291 s from each subject were exposed in vitro to BPDE (4 microm) for 5 h, and the 32P-postlabeling method

292 le Cr(VI) exposure does not change the total BPDE-DNA adduct formation, it significantly inhibited th

293 eactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-B

294 de (7-hydroxyl and epoxide oxygen are trans, BPDE-2) has been determined in Chinese hamster V79 cells

295 diated suppression of COX-2 expression using BPDE as a tool.

296 ed the hypothesis that the level of in vitro BPDE-induced adducts is associated with risk of lung can

297 iously reported association between in vitro BPDE-induced DNA adduct levels and SCCHN risk, and the a

298 nt association between the level of in vitro BPDE-induced DNA adducts and risk for lung cancer sugges

299 treatment of RAR-beta(2)-positive cells with BPDE and the MEK1/2 inhibitor U0126 caused little change

300 luble Cdc45) were reduced concomitantly with BPDE-induced Chk1 activation and inhibition of DNA synth