;PMID: 2766464 ;source_file_1020.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..39] = [t:0..39] ;1)sentence:[e:45..262] = [t:45..262] ;2)section:[e:266..351] = [t:266..351] ;3)section:[e:355..475] = [t:355..475] ;4)sentence:[e:479..707] = [t:479..707] ;5)sentence:[e:708..1156] = [t:708..1156] ;6)sentence:[e:1157..1332] = [t:1157..1332] ;7)sentence:[e:1333..1481] = [t:1333..1481] ;8)sentence:[e:1482..1633] = [t:1482..1633] ;9)sentence:[e:1634..1792] = [t:1634..1792] ;10)sentence:[e:1793..2008] = [t:1793..2008] ;11)sentence:[e:2009..2108] = [t:2009..2108] ;12)section:[e:2112..2156] = [t:2112..2155] ;Sentence Matching Errors ;ERROR_Section end mismatch[e:2112..2156][t:2112..2155] ;Token/POS Errors ;ERROR_Token in entity file but not tree[2155..2156] ] ;section 0 Span:0..39 ;Carcinogenesis. 1989 Sep;10(9):1719-24. (SEC (FRAG (NNP:[0..14] Carcinogenesis) (,:[14..15] .) (CD:[16..20] 1989) (::[21..28] Sep;10-LRB-) (CD:[28..29] 9) (-RRB-:[29..30] -RRB-) (CD:[30..35] :1719) (::[35..36] -) (CD:[36..38] 24) (.:[38..39] .))) ;sentence 1 Span:45..262 ;Lack of promoting effect of clonazepam on the development of ;N-nitrosodiethylamine-initiated hepatocellular tumors in mice is correlated ;with its inability to inhibit cell-to-cell communication in mouse ;hepatocytes. ;[73..83]:substance:"clonazepam" ;[107..128]:substance:"N-nitrosodiethylamine" (SENT (S-HLN (NP-SBJ-1 (NP (NN:[45..49] Lack)) (PP (IN:[50..52] of) (NP (NP (VBG:[53..62] promoting) (NN:[63..69] effect)) (PP (IN:[70..72] of) (NP (NN:[73..83] clonazepam))) (PP (IN:[84..86] on) (NP (NP (DT:[87..90] the) (NN:[91..102] development)) (PP (IN:[103..105] of) (NP (ADJP (NN:[107..128] N-nitrosodiethylamine) (HYPH:[128..129] -) (VBN:[129..138] initiated)) (JJ:[139..153] hepatocellular) (NNS:[154..160] tumors))) (PP-LOC (IN:[161..163] in) (NP (NNS:[164..168] mice)))))))) (VP (VBZ:[169..171] is) (VP (JJ:[172..182] correlated) (NP-1 (-NONE-:[182..182] *)) (PP-CLR (IN:[183..187] with) (NP (PRP$:[189..192] its) (NN:[193..202] inability) (S (NP-SBJ (-NONE-:[202..202] *)) (VP (TO:[203..205] to) (VP (VB:[206..213] inhibit) (NP (NML (NML (NN:[214..218] cell)) (HYPH:[218..219] -) (PP (TO:[219..221] to) (HYPH:[221..222] -) (NP (NN:[222..226] cell)))) (NN:[227..240] communication)) (PP-LOC (IN:[241..243] in) (NP (NN:[244..249] mouse) (NNS:[250..261] hepatocytes)))))))))) (.:[261..262] .))) ;section 2 Span:266..351 ;Diwan BA, Lubet RA, Nims RW, Klaunig JE, Weghorst CM, Henneman JR, Ward JM, ;Rice JM. (SEC (FRAG (NNP:[266..271] Diwan) (NNP:[272..274] BA) (,:[274..275] ,) (NNP:[276..281] Lubet) (NNP:[282..284] RA) (,:[284..285] ,) (NNP:[286..290] Nims) (NNP:[291..293] RW) (,:[293..294] ,) (NNP:[295..302] Klaunig) (NNP:[303..305] JE) (,:[305..306] ,) (NNP:[307..315] Weghorst) (NNP:[316..318] CM) (,:[318..319] ,) (NNP:[320..328] Henneman) (NNP:[329..331] JR) (,:[331..332] ,) (NNP:[333..337] Ward) (NNP:[338..340] JM) (,:[340..341] ,) (NNP:[342..346] Rice) (NNPS:[348..350] JM) (.:[350..351] .))) ;section 3 Span:355..475 ;Biological Carcinogenesis and Development Program Resources, Inc., National ;Cancer Institute, Frederick, MD 21701-1013. (SEC (FRAG (NNP:[355..365] Biological) (NNP:[366..380] Carcinogenesis) (CC:[381..384] and) (NNP:[385..396] Development) (NNP:[397..404] Program) (NNPS:[405..414] Resources) (,:[414..415] ,) (NNP:[416..420] Inc.) (,:[420..421] ,) (NNP:[422..430] National) (NNP:[432..438] Cancer) (NNP:[439..448] Institute) (,:[448..449] ,) (NNP:[450..459] Frederick) (,:[459..460] ,) (NNP:[461..463] MD) (CD:[464..469] 21701) (::[469..470] -) (CD:[470..474] 1013) (.:[474..475] .))) ;sentence 4 Span:479..707 ;The tumor-promoting ability of clonazepam (CZP), a widely used benzodiazepine ; anticonvulsant, was investigated in an in vivo mouse liver tumor promotion ;assay and an in vitro mouse hepatocyte intercellular communication assay. ;[510..520]:substance:"clonazepam" ;[522..525]:substance:"CZP" ;[542..572]:substance:"benzodiazepine anticonvulsant" (SENT (S (NP-SBJ-1 (NP (DT:[479..482] The) (ADJP (NN:[483..488] tumor) (HYPH:[488..489] -) (VBG:[489..498] promoting)) (NN:[499..506] ability)) (PP (IN:[507..509] of) (NP (NP (NP (NN:[510..520] clonazepam)) (NP (-LRB-:[521..522] -LRB-) (NN:[522..525] CZP) (-RRB-:[525..526] -RRB-))) (,:[526..527] ,) (NP (DT:[528..529] a) (ADJP (RB:[530..536] widely) (VBN:[537..541] used)) (NN:[542..556] benzodiazepine) (NN:[558..572] anticonvulsant))))) (,:[572..573] ,) (VP (VBD:[574..577] was) (VP (VBN:[578..590] investigated) (NP-1 (-NONE-:[590..590] *)) (PP (IN:[591..593] in) (NP (NP (DT:[594..596] an) (ADJP (FW:[597..599] in) (FW:[600..604] vivo)) (NML (NN:[605..610] mouse) (NN:[611..616] liver)) (NML (NN:[617..622] tumor) (NN:[623..632] promotion)) (NN:[633..638] assay)) (CC:[640..643] and) (NP (DT:[644..646] an) (ADJP (FW:[647..649] in) (FW:[650..655] vitro)) (NML (NN:[656..661] mouse) (NN:[662..672] hepatocyte)) (NML (JJ:[673..686] intercellular) (NN:[687..700] communication)) (NN:[701..706] assay)))))) (.:[706..707] .))) ;sentence 5 Span:708..1156 ;The development of preneoplastic hepatocellular foci of cellular alteration ;and hepatocellular neoplasms was studied in male B6C3F1 mice initiated, at 5 ;weeks of age, with a single i.p. injection of N-nitrosodiethylamine (NDEA; ;90 mg/kg body weight) in tricaprylin, followed by administration of either ;phenobarbital (PB; 0.05%) or CZP (0.068% or 0.136%) in diet beginning 2 ;weeks after carcinogen injection and continuing to 60 weeks of age. ;[861..862]:quantitative-value:"5" ;[863..868]:quantitative-units:"weeks" ;[910..931]:substance:"N-nitrosodiethylamine" ;[933..937]:substance:"NDEA" ;[939..941]:quantitative-value:"90" ;[942..960]:quantitative-units:"mg/kg body weight" ;[965..976]:substance:"tricaprylin" ;[1015..1028]:substance:"phenobarbital" ;[1031..1033]:substance:"PB" ;[1035..1040]:quantitative-value:"0.05%" ;[1045..1048]:substance:"CZP" ;[1050..1056]:quantitative-value:"0.068%" ;[1060..1066]:quantitative-value:"0.136%" ;[1086..1087]:quantitative-value:"2" ;[1088..1093]:quantitative-units:"weeks" ;[1100..1110]:substance:"carcinogen" ;[1140..1142]:quantitative-value:"60" ;[1143..1148]:quantitative-units:"weeks" (SENT (S (NP-SBJ-1 (NP (DT:[708..711] The) (NN:[713..724] development)) (PP (IN:[725..727] of) (NP (NP (NP (JJ:[728..741] preneoplastic) (JJ:[742..756] hepatocellular) (NNS:[757..761] foci)) (PP (IN:[762..764] of) (NP (JJ:[765..773] cellular) (NN:[774..784] alteration)))) (CC:[785..788] and) (NP (JJ:[790..804] hepatocellular) (NNS:[805..814] neoplasms))))) (VP (VBD:[815..818] was) (VP (VBN:[819..826] studied) (NP-1 (-NONE-:[826..826] *)) (PP-LOC (IN:[827..829] in) (NP (NP (JJ:[830..834] male) (NN:[835..841] B6C3F1) (NNS:[842..846] mice)) (VP (VBN:[847..856] initiated) (NP (-NONE-:[856..856] *)) (,:[856..857] ,) (PP-TMP (IN:[858..860] at) (NP (NP (CD:[861..862] 5) (NNS:[863..868] weeks)) (PP (IN:[870..872] of) (NP (NN:[873..876] age))))) (,:[876..877] ,) (PP-MNR (IN:[878..882] with) (NP (NP (NP (DT:[883..884] a) (JJ:[885..891] single) (NN:[892..896] i.p.) (NN:[897..906] injection)) (PP (IN:[907..909] of) (NP (NP (NP (NN:[910..931] N-nitrosodiethylamine)) (NP (-LRB-:[932..933] -LRB-) (NN:[933..937] NDEA)) (PRN (::[937..938] ;) (NP (NP (CD:[939..941] 90) (NN:[942..944] mg)) (PP (SYM:[944..945] /) (NP (NN:[945..947] kg) (NN:[949..953] body) (NN:[954..960] weight)))) (-RRB-:[960..961] -RRB-))) (PP (IN:[962..964] in) (NP (NN:[965..976] tricaprylin)))))) (,:[976..977] ,) (VP (VBN:[978..986] followed) (NP (-NONE-:[986..986] *)) (PP (IN:[987..989] by) (NP-LGS (NP (NP (NN:[990..1004] administration)) (PP (IN:[1005..1007] of) (NP (CC:[1008..1014] either) (NP (NP (NN:[1015..1028] phenobarbital)) (NP (-LRB-:[1030..1031] -LRB-) (NN:[1031..1033] PB)) (::[1033..1034] ;) (PRN (NP (CD:[1035..1039] 0.05) (NN:[1039..1040] %)) (-RRB-:[1040..1041] -RRB-))) (CC:[1042..1044] or) (NP (NN:[1045..1048] CZP) (PRN (-LRB-:[1049..1050] -LRB-) (NP (NP (CD:[1050..1055] 0.068) (NN:[1055..1056] %)) (CC:[1057..1059] or) (NP (CD:[1060..1065] 0.136) (NN:[1065..1066] %))) (-RRB-:[1066..1067] -RRB-))))) (PP (IN:[1068..1070] in) (NP (NN:[1071..1075] diet)))) (VP (VP (VBG:[1076..1085] beginning) (NP-TMP (NP (CD:[1086..1087] 2) (NNS:[1088..1093] weeks)) (PP (IN:[1094..1099] after) (NP (NN:[1100..1110] carcinogen) (NN:[1112..1121] injection))))) (CC:[1122..1125] and) (VP (VBG:[1126..1136] continuing) (PP-TMP (TO:[1137..1139] to) (NP (NP (CD:[1140..1142] 60) (NNS:[1143..1148] weeks)) (PP (IN:[1149..1151] of) (NP (NN:[1152..1155] age))))))))))))))))) (.:[1155..1156] .))) ;sentence 6 Span:1157..1332 ;Several mice from each group were killed after 9, 21, 33 or 53 weeks on test ;diet, and portions of liver and other organs were fixed in formalin and ;examined histologically. ;[1205..1206]:quantitative-value:"9" ;[1208..1210]:quantitative-value:"21" ;[1212..1214]:quantitative-value:"33" ;[1218..1220]:quantitative-value:"53" ;[1221..1226]:quantitative-units:"weeks" ;[1295..1303]:substance:"formalin" (SENT (S (S (NP-SBJ-2 (NP (JJ:[1157..1164] Several) (NNS:[1165..1169] mice)) (PP (IN:[1170..1174] from) (NP (DT:[1175..1179] each) (NN:[1180..1185] group)))) (VP (VBD:[1186..1190] were) (VP (VBN:[1192..1198] killed) (NP-2 (-NONE-:[1198..1198] *)) (PP-TMP (IN:[1199..1204] after) (NP (NP (NP (CD:[1205..1206] 9) (NML-1 (-NONE-:[1206..1206] *P*))) (,:[1206..1207] ,) (NP (CD:[1208..1210] 21) (NML-1 (-NONE-:[1210..1210] *P*))) (,:[1210..1211] ,) (NP (CD:[1212..1214] 33) (NML-1 (-NONE-:[1214..1214] *P*))) (CC:[1215..1217] or) (NP (CD:[1218..1220] 53) (NML-1 (NNS:[1221..1226] weeks)))) (PP (IN:[1227..1229] on) (NP (NN:[1230..1234] test) (NN:[1235..1239] diet)))))))) (,:[1239..1240] ,) (CC:[1241..1244] and) (S (NP-SBJ-3 (NP (NNS:[1245..1253] portions)) (PP (IN:[1254..1256] of) (NP (NP (NN:[1257..1262] liver)) (CC:[1263..1266] and) (NP (JJ:[1267..1272] other) (NNS:[1274..1280] organs))))) (VP (VBD:[1281..1285] were) (VP (VP (VBN:[1286..1291] fixed) (NP-3 (-NONE-:[1291..1291] *)) (PP (IN:[1292..1294] in) (NP (NN:[1295..1303] formalin)))) (CC:[1304..1307] and) (VP (VBN:[1308..1316] examined) (NP-3 (-NONE-:[1316..1316] *)) (ADVP (RB:[1317..1331] histologically)))))) (.:[1331..1332] .))) ;sentence 7 Span:1333..1481 ;Unlike PB, CZP did not promote the development of preneoplastic ;hepatocellular foci or neoplasms (adenomas and carcinomas) in NDEA-initiated ;mice. ;[1340..1342]:substance:"PB" ;[1344..1347]:substance:"CZP" ;[1461..1465]:substance:"NDEA" (SENT (S (PP (IN:[1333..1339] Unlike) (NP (NN:[1340..1342] PB))) (,:[1342..1343] ,) (NP-SBJ (NN:[1344..1347] CZP)) (VP (VBD:[1348..1351] did) (RB:[1353..1356] not) (VP (VB:[1357..1364] promote) (NP (NP (DT:[1365..1368] the) (NN:[1369..1380] development)) (PP (IN:[1381..1383] of) (NP (NP (JJ:[1384..1397] preneoplastic) (JJ:[1398..1412] hepatocellular) (NNS:[1413..1417] foci)) (CC:[1418..1420] or) (NP (NNS:[1421..1430] neoplasms) (PRN (-LRB-:[1432..1433] -LRB-) (NP (NNS:[1433..1441] adenomas) (CC:[1442..1445] and) (NNS:[1446..1456] carcinomas)) (-RRB-:[1456..1457] -RRB-)))))) (PP-LOC (IN:[1458..1460] in) (NP (ADJP (NN:[1461..1465] NDEA) (HYPH:[1465..1466] -) (VBN:[1466..1475] initiated)) (NNS:[1476..1480] mice))))) (.:[1480..1481] .))) ;sentence 8 Span:1482..1633 ;Following limited (2 weeks) dietary exposure at 0.15%, CZP was a potent ;inducer of hepatic P450IIB1-mediated alkoxyresorufin O-dealkylase ;activities. ;[1501..1502]:quantitative-value:"2" ;[1503..1508]:quantitative-units:"weeks" ;[1531..1536]:quantitative-value:"0.15%" ;[1538..1541]:substance:"CZP" ;[1555..1562]:substance:"inducer" ;[1574..1582]:cyp450:"P450IIB1" ;[1593..1621]:substance:"alkoxyresorufin O-dealkylase" (SENT (S (PP (VBG:[1482..1491] Following) (NP (NP (VBN:[1492..1499] limited) (PRN (-LRB-:[1500..1501] -LRB-) (NP (CD:[1501..1502] 2) (NNS:[1503..1508] weeks)) (-RRB-:[1508..1509] -RRB-)) (JJ:[1511..1518] dietary) (NN:[1519..1527] exposure)) (PP (IN:[1528..1530] at) (NP (CD:[1531..1535] 0.15) (NN:[1535..1536] %))))) (,:[1536..1537] ,) (NP-SBJ (NN:[1538..1541] CZP)) (VP (VBD:[1542..1545] was) (NP-PRD (NP (DT:[1546..1547] a) (JJ:[1548..1554] potent) (NN:[1555..1562] inducer)) (PP (IN:[1563..1565] of) (NP (JJ:[1566..1573] hepatic) (ADJP (NN:[1574..1582] P450IIB1) (HYPH:[1582..1583] -) (VBN:[1583..1591] mediated)) (NML (NN:[1593..1608] alkoxyresorufin) (NN:[1609..1621] O-dealkylase)) (NNS:[1622..1632] activities))))) (.:[1632..1633] .))) ;sentence 9 Span:1634..1792 ;In contrast, the degree of induction in hepatic tissue from mice fed 0.136% ;CZP for 53 weeks was markedly lower than that in mice fed 0.05% PB for 53 ;weeks. ;[1704..1710]:quantitative-value:"0.136%" ;[1711..1714]:substance:"CZP" ;[1719..1721]:quantitative-value:"53" ;[1722..1727]:quantitative-units:"weeks" ;[1770..1775]:quantitative-value:"0.05%" ;[1776..1778]:substance:"PB" ;[1783..1785]:quantitative-value:"53" ;[1786..1791]:quantitative-units:"weeks" (SENT (S (PP (IN:[1634..1636] In) (NP (NN:[1637..1645] contrast))) (,:[1645..1646] ,) (NP-SBJ (NP (DT:[1647..1650] the) (NN:[1651..1657] degree)) (PP (IN:[1658..1660] of) (NP (NN:[1661..1670] induction))) (PP-LOC (IN:[1671..1673] in) (NP (NP (JJ:[1675..1682] hepatic) (NN:[1683..1689] tissue)) (PP (IN:[1690..1694] from) (NP (NP (NNS:[1695..1699] mice)) (VP (VBN:[1700..1703] fed) (NP (-NONE-:[1703..1703] *)) (NP (NML (CD:[1704..1709] 0.136) (NN:[1709..1710] %)) (NN:[1711..1714] CZP)) (PP-TMP (IN:[1715..1718] for) (NP (CD:[1719..1721] 53) (NNS:[1722..1727] weeks))))))))) (VP (VBD:[1728..1731] was) (ADJP-PRD (ADJP (RB:[1732..1740] markedly) (JJR:[1741..1746] lower)) (PP (IN:[1747..1751] than) (NP (NP (DT:[1753..1757] that)) (PP-LOC (IN:[1758..1760] in) (NP (NP (NNS:[1761..1765] mice)) (VP (VBD:[1766..1769] fed) (NP (-NONE-:[1769..1769] *)) (NP (NML (CD:[1770..1774] 0.05) (NN:[1774..1775] %)) (NN:[1776..1778] PB)) (PP-TMP (IN:[1779..1782] for) (NP (CD:[1783..1785] 53) (NNS:[1786..1791] weeks)))))))))) (.:[1791..1792] .))) ;sentence 10 Span:1793..2008 ;In the in vitro assay, diazepam, a strong tumor promoter in mouse liver, ;significantly inhibited mouse hepatocyte gap junctional intercellular ;communication, while CZP had no significant effect on this parameter. ;[1816..1824]:substance:"diazepam" ;[1842..1850]:substance:"promoter" ;[1959..1962]:substance:"CZP" (SENT (S (PP (IN:[1793..1795] In) (NP (DT:[1796..1799] the) (ADJP (FW:[1800..1802] in) (FW:[1803..1808] vitro)) (NN:[1809..1814] assay))) (,:[1814..1815] ,) (NP-SBJ (NP (NN:[1816..1824] diazepam)) (,:[1824..1825] ,) (NP (NP (DT:[1826..1827] a) (JJ:[1829..1835] strong) (NN:[1836..1841] tumor) (NN:[1842..1850] promoter)) (PP-LOC (IN:[1851..1853] in) (NP (NN:[1854..1859] mouse) (NN:[1860..1865] liver))))) (,:[1865..1866] ,) (ADVP (RB:[1867..1880] significantly)) (VP (VBD:[1881..1890] inhibited) (NP (NML (NN:[1891..1896] mouse) (NN:[1897..1907] hepatocyte)) (ADJP (NN:[1909..1912] gap) (JJ:[1913..1923] junctional)) (JJ:[1924..1937] intercellular) (NN:[1938..1951] communication)) (,:[1951..1952] ,) (SBAR-ADV (IN:[1953..1958] while) (S (NP-SBJ (NN:[1959..1962] CZP)) (VP (VBD:[1963..1966] had) (NP (NP (DT:[1967..1969] no) (JJ:[1970..1981] significant) (NN:[1982..1988] effect)) (PP (IN:[1990..1992] on) (NP (DT:[1993..1997] this) (NN:[1998..2007] parameter)))))))) (.:[2007..2008] .))) ;sentence 11 Span:2009..2108 ;Thus, CZP, a drug structurally related to diazepam, is inactive as a liver ;tumor promoter in mice. ;[2015..2018]:substance:"CZP" ;[2022..2026]:substance:"drug" ;[2051..2059]:substance:"diazepam" ;[2091..2099]:substance:"promoter" (SENT (S (ADVP (RB:[2009..2013] Thus)) (,:[2013..2014] ,) (NP-SBJ (NP (NN:[2015..2018] CZP)) (,:[2018..2019] ,) (NP (NP (DT:[2020..2021] a) (NN:[2022..2026] drug)) (VP (ADVP (RB:[2027..2039] structurally)) (JJ:[2040..2047] related) (NP (-NONE-:[2047..2047] *)) (PP-CLR (TO:[2048..2050] to) (NP (NN:[2051..2059] diazepam)))))) (,:[2059..2060] ,) (VP (VBZ:[2061..2063] is) (ADJP-PRD (JJ:[2065..2073] inactive)) (PP (IN:[2074..2076] as) (NP (DT:[2077..2078] a) (JJ:[2079..2084] liver) (NN:[2085..2090] tumor) (NN:[2091..2099] promoter))) (PP-LOC (IN:[2100..2102] in) (NP (NNS:[2103..2107] mice)))) (.:[2107..2108] .))) ;section 12 Span:2112..2155 ;PMID: 2766464 [PubMed - indexed for MEDLINE (SEC (FRAG (NNP:[2112..2116] PMID) (::[2116..2117] :) (CD:[2118..2125] 2766464) (-LRB-:[2126..2127] -LSB-) (NNP:[2127..2133] PubMed) (::[2134..2135] -) (VBN:[2136..2143] indexed) (IN:[2144..2147] for) (NNP:[2148..2155] MEDLINE))) ;ERROR_Orphan Text from EOF Tree File[2155..EOF] ] (ORPH -RSB-)