ライフサイエンスコーパス: MNNG

1 MNNG induced 14 predominant hot spots, all which were G:

2 MNNG induced the formation of PCNA complexes with MSH6 a

3 MNNG-induced nuclear exclusion of the cell cycle regulat

4 Thirteen of these 14 MNNG-induced hot spots were found among the in vivo set,

5 orylation of the p53 residue serine 15 after MNNG.

6 3, and lack of activation of caspase 3 after MNNG treatment.

7 haracteristics and cell cycle analysis after MNNG treatment were ascertained in seven MMR-deficient a

8 , SW480, cell death occurred five days after MNNG treatment.

9 MSH2, and this interaction is enhanced after MNNG exposure, supporting the notion that the MMR system

10 tant increase in the p53 protein level after MNNG treatment.

11 occurred quite rapidly (within 30 min) after MNNG treatment, suggesting that DNA strand breaks that a

12 and GADD45alpha protein up-regulation after MNNG exposure prompted us to examine c-Abl/p73alpha/GADD

13 ucing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following gamma

14 tment of cells with the DNA-alkylating agent MNNG.

15 -)), were treated with the methylating agent MNNG to create a level of O(6)-methylguanine in cellular

16 istance to the cytotoxicity of the alkylator MNNG.

17 pathways comediate both the constitutive and MNNG-accelerated degradation of Mgt1.

18 primosome) genes are as sensitive to MMS and MNNG as alkA tag bacteria.

19 ensitive to the cytotoxic effects of MMS and MNNG as the most base excision repair (BER)-deficient (a

20 lpha induction was impaired in both UVB- and MNNG-treated C/EBPbeta(-/-) fibroblasts.

21 Finally, when p21 degradation was blocked, MNNG treatment resulted in reduced recruitment of MMR pr

22 t otherwise results from PARP1 activation by MNNG or H(2)O(2).

23 f the BBL42-BBL28 operon was not affected by MNNG.

24 the response pathway to DNA damage caused by MNNG.

25 PAR synthesis and apoptotic death induced by MNNG in H2AX-deficient cells are due to impaired activat

26 ro, but it protected E. coli from killing by MNNG even in the presence of BG and had an ED50 for the

27 ve in reducing mutations and cell killing by MNNG.

28 In DNA methylated by MNNG, MMR action is the result of MutS recognition of O6

29 dependent G(2) arrest responses triggered by MNNG are dependent on a human MLH1/c-Abl/GADD45alpha sig

30 ranscribed and expression was upregulated by MNNG.

31 MMR-deficient cells fail to detect MNNG-induced DNA damage, resulting in the survival of "m

32 Twelve different MNNG-induced GC-->AT transitions were reproducibly obser

33 downstream mechanism through which high-dose MNNG establishes G(2) arrest.

34 ia, mutated (ATM)-deficient cells, high-dose MNNG treatment activates G(2) arrest through an ATM-inde

35 r cell-cycle arrest in response to high-dose MNNG treatment; however, ATR deficiency and decreased Ch

36 dent of ATM and MMR in response to high-dose MNNG, unlike the response to moderate doses of this drug

37 ncrease poly(ADP-ribose) accumulation during MNNG exposure.

38 nd potency as a neuroprotective agent during MNNG incubations, with the rank order of potency being m

39 ctivated in a MMR-dependent manner following MNNG, and several also require ATM kinase activity.

40 and A:T-->G:C mutator phenotype typical for MNNG-induced unrepaired lesions.

41 de synthesis ISP-1 protected LME6 cells from MNNG-triggered cell death.

42 d found that CRE-binding protein (CREB) from MNNG-treated cells differentially up-regulates the promo

43 the RPc assembled with nuclear extract from MNNG-treated and control HeLa cells.

44 lso able to produce moderate protection from MNNG when expressed in E. coli.

45 the exact nature of the mechanism governing MNNG-induced G2/M arrest and how MMR mechanistically par

46 f the N-Methyl-N'-nitro-N-nitroso-guanidine (MNNG) HOS transforming gene (MET) oncogene as two princi

47 UV or 1-methyl-3-nitro-1-nitroso-guanidine (MNNG).

48 xokinase and inhibits hexokinase activity in MNNG-treated cortical neurons.

49 1-DNA covalent complexes are also induced in MNNG-treated CHO cells constitutively lacking the AGT en

50 AT transitions were reproducibly observed in MNNG-treated cells at mutant fractions between 2 x 10(-6

51 We observed that in MNNG-treated normal human fibroblasts, up-regulation and

52 amaging agents, including ultraviolet light, MNNG and bleomycin.

53 Furthermore, highly metastatic MNNG-HOS cells have increased levels of beta4 integrin.

54 A single dose of 4 microM MNNG (survival, 0.85) induced a mutant fraction of 8 x 1

55 tion in N-methyl-N-nitroso-N-nitroguanidine (MNNG)-treated cortical neurons.

56 microg of 1-methyl-3-nitroso-nitroguanidine (MNNG) ml(-1).

57 ultivated 1-methyl-3-nitroso-nitroguanidine (MNNG)-treated and untreated spirochetes and during infec

58 tory strain that carries a nitrosoguanidine (MNNG)-induced mutation enabling it to accept DNA from Es

59 N-Methyl-N'-nitro-N'-nitrosoguanidine (MNNG) is a DNA-methylating agent, and deficiency in mism

60 agent N-methyl-N'-nitro-N- nitrosoguanidine (MNNG) also triggers up-regulation and phosphorylation of

61 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and antimetabolite 6-thioguanine (6-TG).

62 (MMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and mechlorethamine HCl (HN2), oxidizing agents, s

63 uch as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methane sulfonate (MMS) produce a wide

64 g agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell

65 uch as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are known to covalently link alkyl groups at the p

66 sed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 10(-5) mol/L for 48 hours, the treated cells gr

67 e from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by activating ATR (ataxia telangiectasia-Rad3-rela

68 sourea N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) elicit a G2/M checkpoint response via a mismatch r

69 ing by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) even in the presence of BG and that the AGT activi

70 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) exhibited a microsatellite instability (MIN) assoc

71 microM N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for increasing lengths of time and was confirmed b

72 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces expression of the endogenous mammalian DNA

73 N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a direct-acting monofunctional alkylator.

74 uch as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on DNA.

75 agents N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 3-morpholinosydnonimine (SIN-1).

76 d with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resulted in a concentration dependent increase in

77 lowing N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment.

78 agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) when expressed in Escherichia coli cells lacking e

79 ion of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) while abrogation of such repair results in drug re

80 te and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)) was dependent on H2AX dosage, and H2AX null cells

81 ity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a functional analogue of temozolomide.

82 luding N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a potent carcinogen.

83 agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the AGT inhibitor, O6-benzylguanine (BG).

84 notoxin N-methyl-N-nitro-N-nitrosoguanidine (MNNG), both cell lines underwent cytolysis in a very sim

85 sed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but normal human oral keratinocytes cannot transf

86 ure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), Msh2 deficient mice show a reduced apoptotic resp

87 c drug N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), robustly activate the DNA damage-responsive G(2)

88 poxide, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), t-butyl hydrogen peroxide, and UV irradiation and

89 ged by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which generates O(6)-methylguanine and O(4)-methy

90 ion by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which triggers the MMR system.

91 luding N-methyl-N'-nitro-N-nitrosoguanidine (MNNG),which is known to cause colon cancer in animals, a

92 map of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations was determined in human lymphobl

93 ut not N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced PARP-1 hyperactivation and cell death.

94 suring N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced point mutations in a 121 bp sequence of th

95 und or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced, in NHOK expressing the HPV-16 oncoprotein

96 )- and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated fibroblasts showed increased binding of C/

97 agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

98 d with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

99 nse to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

100 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

101 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

102 agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); (b) repair methylated DNA in vitro; (c) bind to o

103 atin and N-methyl-N'-nitro-nitrosoguanidine (MNNG, a common DNA-alkylating chemotherapeutic agent).

104 Chk2 are both required components for normal MNNG-induced G2 arrest.

105 mutation are resistant to cisplatin, but not MNNG, toxicity.

106 biochemical approaches, we failed to observe MNNG-induced apoptosis in normal human fibroblasts, sugg

107 However, our ability to observe MNNG-induced mitochondrial mutations above the high leve

108 d nine mutants resistant to a combination of MNNG and BG, and the survival of these mutants was as mu

109 out not to be an adventitious consequence of MNNG mutagenesis, but rather had arisen in RN450, the im

110 ) system; however, exposure to high doses of MNNG overrides the requirement for MMR to trigger G(2) a

111 ficient cells treated with moderate doses of MNNG.

112 air of damaged DNA, we studied the effect of MNNG exposure upon cell cycle progression, expression of

113 ne into HCT-116 cells mimicked the effect of MNNG-induced expression of APC mRNA.

114 inocytes and enhance the mutagenic effect of MNNG.

115 ne regulation is supported by the failure of MNNG to induce APC expression in cell lines either expre

116 The formation of MNNG-induced mutations is almost abolished in the rad30D

117 ecific antibody during the initial 30 min of MNNG treatment.

118 the cytotoxicity but not the mutagenicity of MNNG, presumably as a result of inactivation of both cop

119 The proteins of MNNG-treated dog gallbladder epithelial cells showed inc

120 ere generated in living cells as a result of MNNG treatment and not from mismatch intermediates or DN

121 tion of c-Abl also increased the survival of MNNG-exposed MMR-proficient cells to a level comparable

122 The background or MNNG-induced mutation frequency in NHOK expressing the H

123 eated C/EBPbeta(-/-) fibroblasts with UVB or MNNG.

124 hibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice.

125 nd a clear and reproducible pattern of seven MNNG-induced hotspot mutations was observed within the m

126 Preliminary screening of six MNNG-induced tumors in four adult medaka revealed no mut

127 show, by several different approaches, that MNNG-treated tumor cells do not arrest within the second

128 al experiments supported the conclusion that MNNG-induced hotspot mutations observed were generated i

129 We document that MNNG induces a robust, dose-dependent G2 arrest in MMR a

130 We find that MNNG induces replication-associated DNA double-strand br

131 These results indicate that MNNG activates the G(2) checkpoint through different mec

132 Immunoblotting revealed that MNNG-induced transcription led to increased protein prod

133 We show that MNNG caused rapid degradation of p21, and this involved

134 Here, we show that MNNG exposure results in activation of the cell cycle ch

135 hot spot spectrum and strongly suggest that MNNG-induced hot spots in vitro share a common mutationa

136 polymerase 1 (PARP-1) cleavage suggests that MNNG-induced apoptosis occurs by PARP-1-dependent manner

137 The MNNG spectrum was distinct from the spontaneous mutation

138 g a hypergeometric test for concordance, the MNNG-induced hot spots were found to be a significant su

139 tS and Ada methyltransferase compete for the MNNG-induced O6-methylguanine residues, and MMR-induced

140 tional protein kinase A, is critical for the MNNG-induced up-regulation.

141 vert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary t

142 failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibitio

143 B-1 to the control cell extract mimicked the MNNG-induced up-regulation of transcriptional activity.

144 e found among the in vivo set, and 10 of the MNNG-induced hot spots were among 75 putative in vivo ho

145 All of the MNNG-induced hotspot mutations were G:C to A:T transitio

146 16 oncogenes did not alter the nature of the MNNG-induced mutations (G:C-->A:T), but increased the fr

147 n the purified RPc samples revealed that the MNNG induction is associated with a strong increase in t

148 indicating a role for ATM in triggering the MNNG-induced response.

149 This MNNG-triggered induction of ceramide was not observed in

150 AF1/CIP1), and Gadd45 levels when exposed to MNNG, whereas NHOK expressing the HPV-16 E6 oncogene did

151 rrest cell cycle progression when exposed to MNNG.

152 ransient cell cycle arrest after exposure to MNNG, but the other tested cells did not.

153 ation; second, 3 weeks following exposure to MNNG, where only complete loss of Msh2 results in elevat

154 fd4 ubiquitin ligases were hyperresistant to MNNG but hypersensitive to the toxicity of overexpressed

155 efective cells, resistance of Med1-/- MEF to MNNG was due to a tolerance mechanism because DNA damage

156 s even more substitutions than resistance to MNNG alone.

157 eight, suggesting that maximum resistance to MNNG in the presence of BG requires even more substituti

158 spontaneous mutation rates and resistance to MNNG treatment in vivo.

159 On sequencing surviving clones resistant to MNNG in the presence and absence of BG, we found that a

160 to PhIP, whereas MIN cells are resistant to MNNG.

161 or cannot be ubiquitinated were resistant to MNNG.

162 LH1- and ATM-dependent manner in response to MNNG and perhaps suggests that dysregulation of this sig

163 int to suppress DNA synthesis in response to MNNG, and phosphorylation of SMC1 is required for cellul

164 red for the activation of ATM in response to MNNG.

165 nt MLH1 and ATM, but not ATR, in response to MNNG.

166 ormal and MMR-deficient cells in response to MNNG.

167 nts (alkA tag recBCD) were more sensitive to MNNG and MMS than the single mutants suggesting that hom

168 ressing the human Top1 are more sensitive to MNNG, whereas knock-out Top1 strain cells display some r

169 While MNNG exposure significantly increased the levels of intr

170 With MNNG, significant differences in response were observed

171 Exposure of cells with MNNG caused an 8-12-fold increase in the level of APC mR

172 d LME6, and treatment of the LME6 cells with MNNG resulted in a transient increase in intracellular c

173 n addition, the prophage can be induced with MNNG from some Borrelia isolates that do not naturally p

174 molecules, one of which was methylated with MNNG.

175 ic response patterns were only observed with MNNG, t-butyl hydrogen peroxide, and UV irradiation.

176 -positive cells surviving the treatment with MNNG displayed approximately 15-fold higher mutation fre

177 of deletions and insertions with or without MNNG.