;PMID: 3985627 ;source_file_1925.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..43] = [t:0..43] ;1)sentence:[e:49..210] = [t:49..210] ;2)section:[e:214..288] = [t:214..288] ;3)sentence:[e:292..392] = [t:292..392] ;4)sentence:[e:393..855] = [t:393..855] ;5)sentence:[e:856..1065] = [t:856..1065] ;6)sentence:[e:1066..1345] = [t:1066..1345] ;7)sentence:[e:1346..1762] = [t:1346..1762] ;8)section:[e:1766..1810] = [t:1766..1810] ;section 0 Span:0..43 ;Arch Biochem Biophys. 1985 Apr;238(1):43-8. (SEC (FRAG (NNP:[0..4] Arch) (NNP:[5..12] Biochem) (NNP:[13..20] Biophys) (.:[20..21] .) (CD:[22..26] 1985) (.:[27..34] Apr;238) (-LRB-:[34..35] -LRB-) (CD:[35..36] 1) (-RRB-:[36..37] -RRB-) (CD:[37..40] :43) (::[40..41] -) (CD:[41..43] 8.))) ;sentence 1 Span:49..210 ;Dealkylation of pentoxyresorufin: a rapid and sensitive assay for measuring ;induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in ;the rat. ;[65..81]:substance:"pentoxyresorufin" ;[139..158]:cyp450:"cytochrome(s) P-450" ;[162..175]:substance:"phenobarbital" ;[186..197]:substance:"xenobiotics" (SENT (NP-HLN (NP (NP (NN:[49..61] Dealkylation)) (PP (IN:[62..64] of) (NP (NN:[65..81] pentoxyresorufin)))) (::[81..82] :) (NP (NP (DT:[83..84] a) (ADJP (JJ:[85..90] rapid) (CC:[91..94] and) (JJ:[95..104] sensitive)) (NN:[105..110] assay)) (PP (IN:[111..114] for) (S-NOM (NP-SBJ (-NONE-:[114..114] *)) (VP (VBG:[115..124] measuring) (NP (NP (NN:[126..135] induction)) (PP (IN:[136..138] of) (NP (NN:[139..152] cytochrome-LRB-s-RRB-) (NN:[153..158] P-450))) (PP (IN:[159..161] by) (NP (NP (NN:[162..175] phenobarbital)) (CC:[176..179] and) (NP (JJ:[180..185] other) (NNS:[186..197] xenobiotics))))) (PP-LOC (IN:[198..200] in) (NP (DT:[201..204] the) (NN:[206..209] rat))))))) (.:[209..210] .))) ;section 2 Span:214..288 ;Lubet RA, Mayer RT, Cameron JW, Nims RW, Burke MD, Wolff T, Guengerich FP. (SEC (FRAG (NNP:[214..219] Lubet) (NNP:[220..222] RA) (,:[222..223] ,) (NNP:[224..229] Mayer) (NN:[230..232] RT) (,:[232..233] ,) (NNP:[234..241] Cameron) (NNP:[242..244] JW) (,:[244..245] ,) (NNP:[246..250] Nims) (NNP:[251..253] RW) (,:[253..254] ,) (NNP:[255..260] Burke) (NNP:[261..263] MD) (,:[263..264] ,) (NNP:[265..270] Wolff) (NNP:[271..272] T) (,:[272..273] ,) (NNP:[274..284] Guengerich) (NNP:[285..287] FP) (.:[287..288] .))) ;sentence 3 Span:292..392 ;The O-dealkylation of pentoxyresorufin (7-pentoxyphenoxazone) by rat liver ;microsomes was examined. ;[314..330]:substance:"pentoxyresorufin" ;[332..352]:substance:"7-pentoxyphenoxazone" (SENT (S (NP-SBJ-1 (NP (DT:[292..295] The) (NN:[296..310] O-dealkylation)) (PP (IN:[311..313] of) (NP (NP (NN:[314..330] pentoxyresorufin)) (NP (-LRB-:[331..332] -LRB-) (NN:[332..352] 7-pentoxyphenoxazone) (-RRB-:[352..353] -RRB-)))) (PP (IN:[354..356] by) (NP (NN:[357..360] rat) (NN:[361..366] liver) (NNS:[368..378] microsomes)))) (VP (VBD:[379..382] was) (VP (VBN:[383..391] examined) (NP-1 (-NONE-:[391..391] *)))) (.:[391..392] .))) ;sentence 4 Span:393..855 ;The reaction appeared highly specific for certain phenobarbital inducible ;forms of cytochrome P-450 and was increased 95- to 140-fold by animal ;pretreatment with phenobarbital (75 mg/kg/day, four ip injections) and ;approximately 50-fold by Aroclor 1254 (500 mg/kg, one ip injection) while ;animal pretreatment with 3-methylcholanthrene (50 mg/kg/day, three ip ;injections) resulted in less than a 2-fold increase over the rate detected ;in control microsomes. ;[444..457]:substance:"phenobarbital" ;[477..493]:cyp450:"cytochrome P-450" ;[512..528]:quantitative-value:"95- to 140-fold" ;[557..570]:substance:"phenobarbital" ;[572..574]:quantitative-value:"75" ;[575..584]:quantitative-units:"mg/kg/day" ;[625..632]:quantitative-value:"50-fold" ;[636..648]:substance:"Aroclor 1254" ;[650..653]:quantitative-value:"500" ;[654..659]:quantitative-units:"mg/kg" ;[711..731]:substance:"3-methylcholanthrene" ;[733..735]:quantitative-value:"50" ;[736..745]:quantitative-units:"mg/kg/day" ;[781..799]:quantitative-value:"less than a 2-fold" (SENT (S (S (NP-SBJ-2 (DT:[393..396] The) (NN:[397..405] reaction)) (VP (VP (VBD:[406..414] appeared) (ADJP-PRD (RB:[415..421] highly) (JJ:[422..430] specific) (PP (IN:[431..434] for) (NP (NP (JJ:[435..442] certain) (ADJP (NN:[444..457] phenobarbital) (JJ:[458..467] inducible)) (NNS:[468..473] forms)) (PP (IN:[474..476] of) (NP (NN:[477..487] cytochrome) (NN:[488..493] P-450))))))) (CC:[494..497] and) (VP (VBD:[498..501] was) (VP (VP (VBN:[502..511] increased) (NP-2 (-NONE-:[511..511] *)) (ADVP-EXT=4 (QP (CD:[512..514] 95) (HYPH:[514..515] -) (TO:[516..518] to) (CD:[520..523] 140) (HYPH:[523..524] -)) (RB:[524..528] fold)) (PP-MNR=5 (IN:[529..531] by) (NP (NP (NN:[532..538] animal) (NN:[539..551] pretreatment)) (PP (IN:[552..556] with) (NP (NP (NN:[557..570] phenobarbital)) (PRN (-LRB-:[571..572] -LRB-) (FRAG (NP (NP (CD:[572..574] 75) (NN:[575..577] mg)) (PP (SYM:[577..578] /) (NP (NN:[578..580] kg))) (PP (SYM:[580..581] /) (NP (NN:[581..584] day)))) (,:[584..585] ,) (NP (CD:[586..590] four) (JJ:[591..593] ip) (NNS:[595..605] injections))) (-RRB-:[605..606] -RRB-))))))) (CC:[607..610] and) (VP (ADVP-EXT=4 (QP (RB:[611..624] approximately) (CD:[625..627] 50)) (HYPH:[627..628] -) (RB:[628..632] fold)) (PP-MNR=5 (IN:[633..635] by) (NP (NP (NNP:[636..643] Aroclor) (CD:[644..648] 1254)) (PRN (-LRB-:[649..650] -LRB-) (FRAG (NP (NP (CD:[650..653] 500) (NN:[654..656] mg)) (PP (SYM:[656..657] /) (NP (NN:[657..659] kg)))) (,:[659..660] ,) (NP (CD:[661..664] one) (JJ:[665..667] ip) (NN:[669..678] injection))) (-RRB-:[678..679] -RRB-))))))) (SBAR-ADV (IN:[680..685] while) (S (NP-SBJ (NP (NN:[686..692] animal) (NN:[693..705] pretreatment)) (PP (IN:[706..710] with) (NP (NN:[711..731] 3-methylcholanthrene) (PRN (-LRB-:[732..733] -LRB-) (FRAG (NP (NP (CD:[733..735] 50) (NN:[736..738] mg)) (PP (SYM:[738..739] /) (NP (NN:[739..741] kg))) (PP (SYM:[741..742] /) (NP (NN:[742..745] day)))) (,:[745..746] ,) (NP (CD:[748..753] three) (JJ:[754..756] ip) (NNS:[757..767] injections))) (-RRB-:[767..768] -RRB-))))) (VP (VBD:[769..777] resulted) (PP-CLR (IN:[778..780] in) (NP (NP (QP (JJR:[781..785] less) (IN:[786..790] than) (DT:[791..792] a) (CD:[793..794] 2) (HYPH:[794..795] -) (JJ:[795..799] fold)) (NN:[800..808] increase)) (PP (IN:[809..813] over) (NP (NP (DT:[814..817] the) (NN:[818..822] rate)) (VP (VBN:[824..832] detected) (NP (-NONE-:[832..832] *)) (PP-LOC (IN:[833..835] in) (NP (NN:[836..843] control) (NNS:[844..854] microsomes))))))))))))) (.:[854..855] .))) ;sentence 5 Span:856..1065 ;It was observed that this activity, in microsomes for Aroclor-pretreated ;rats, was dependent on O2 and was inhibited by metyrapone and SKF 525-A, ;indicative of cytochrome(s) P-450 mediation in the reaction. ;[911..918]:substance:"Aroclor" ;[953..955]:substance:"O2" ;[978..988]:substance:"metyrapone" ;[993..1002]:substance:"SKF 525-A" ;[1018..1037]:cyp450:"cytochrome(s) P-450" (SENT (S (NP-SBJ-2 (NP (PRP:[856..858] It)) (SBAR-3 (-NONE-:[858..858] *EXP*))) (VP (VBD:[859..862] was) (VP (VBN:[863..871] observed) (NP-2 (-NONE-:[871..871] *)) (SBAR-3 (IN:[872..876] that) (S (NP-SBJ-1 (NP (DT:[877..881] this) (NN:[882..890] activity)) (,:[890..891] ,) (PP-LOC (IN:[892..894] in) (NP (NP (NNS:[896..906] microsomes)) (PP (IN:[907..910] for) (NP (ADJP (NNP:[911..918] Aroclor) (HYPH:[918..919] -) (VBN:[919..929] pretreated)) (NNS:[930..934] rats)))))) (,:[934..935] ,) (VP (VP (VBD:[936..939] was) (ADJP-PRD (JJ:[940..949] dependent) (PP (IN:[950..952] on) (NP (NN:[953..955] O2))))) (CC:[956..959] and) (VP (VBD:[960..963] was) (VP (VBN:[964..973] inhibited) (NP-1 (-NONE-:[973..973] *)) (PP (IN:[974..976] by) (NP-LGS (NP (NN:[978..988] metyrapone)) (CC:[989..992] and) (NP (NN:[993..996] SKF) (CD:[997..1002] 525-A)))) (,:[1002..1003] ,) (S-ADV (NP-SBJ (-NONE-:[1003..1003] *)) (ADJP-PRD (JJ:[1004..1014] indicative) (PP (IN:[1015..1017] of) (NP (NP (NML (NN:[1018..1031] cytochrome-LRB-s-RRB-) (NN:[1032..1037] P-450)) (NN:[1038..1047] mediation)) (PP-LOC (IN:[1048..1050] in) (NP (DT:[1051..1054] the) (NN:[1056..1064] reaction)))))))))))))) (.:[1064..1065] .))) ;sentence 6 Span:1066..1345 ;When antibodies directed against purified cytochrome(s) P-450s were employed ;to inhibit the pentoxyresorufin O-dealkylation reaction, antibodies to ;P-450PB-B greatly inhibited the reaction (greater than 90%), while antibodies ;to P-450PB-C or P-450PB/PCN-E had minimal effects. ;[1071..1081]:substance:"antibodies" ;[1108..1128]:cyp450:"cytochrome(s) P-450s" ;[1159..1175]:substance:"pentoxyresorufin" ;[1201..1211]:substance:"antibodies" ;[1216..1225]:cyp450:"P-450PB-B" ;[1258..1274]:quantitative-value:"greater than 90%" ;[1283..1293]:substance:"antibodies" ;[1298..1307]:cyp450:"P-450PB-C" ;[1311..1318]:cyp450:"P-450PB" ;[1311..1316]...[1319..1324]:cyp450:"P-450"..."PCN-E" (SENT (S (SBAR-ADV (WHADVP-2 (WRB:[1066..1070] When)) (S (NP-SBJ-1 (NP (NNS:[1071..1081] antibodies)) (VP (VBN:[1082..1090] directed) (NP (-NONE-:[1090..1090] *)) (PP (IN:[1091..1098] against) (NP (VBN:[1099..1107] purified) (NNS:[1108..1121] cytochrome-LRB-s-RRB-) (NNS:[1122..1128] P-450s))))) (VP (VBD:[1129..1133] were) (VP (VBN:[1135..1143] employed) (NP-1 (-NONE-:[1143..1143] *)) (S-PRP (NP-SBJ (-NONE-:[1143..1143] *)) (VP (TO:[1144..1146] to) (VP (VB:[1147..1154] inhibit) (NP (DT:[1155..1158] the) (NN:[1159..1175] pentoxyresorufin) (NN:[1176..1190] O-dealkylation) (NN:[1191..1199] reaction))))) (ADVP-TMP-2 (-NONE-:[1199..1199] *T*)))))) (,:[1199..1200] ,) (NP-SBJ (NP (NNS:[1201..1211] antibodies)) (PP (TO:[1212..1214] to) (NP (NN:[1216..1225] P-450PB-B)))) (ADVP (RB:[1226..1233] greatly)) (VP (VBD:[1234..1243] inhibited) (NP (DT:[1244..1247] the) (NN:[1248..1256] reaction)) (PRN (-LRB-:[1257..1258] -LRB-) (ADJP (ADJP (JJR:[1258..1265] greater)) (PP (IN:[1266..1270] than) (NP (CD:[1271..1273] 90) (NN:[1273..1274] %)))) (-RRB-:[1274..1275] -RRB-)) (,:[1275..1276] ,) (SBAR-ADV (IN:[1277..1282] while) (S (NP-SBJ (NP (NNS:[1283..1293] antibodies)) (PP (TO:[1294..1296] to) (NP (NP (NN:[1298..1307] P-450PB-C)) (CC:[1308..1310] or) (NP (NN:[1311..1316] P-450) (NN:[1316..1318] PB) (SYM:[1318..1319] /) (NN:[1319..1324] PCN-E))))) (VP (VBD:[1325..1328] had) (NP (JJ:[1329..1336] minimal) (NNS:[1337..1344] effects)))))) (.:[1344..1345] .))) ;sentence 7 Span:1346..1762 ;Assay of hepatic microsomes from rats which were pretreated with varying ;doses of phenobarbital (0.9-75 mg/kg/day, four ip injections) indicated that ;while aminopyrine-N-demethylase activity was induced only 2-fold at the ;maximum dose (75 mg/kg/day), pentoxyresorufin O-dealkylase activity was ;induced approximately 140-fold at this dose and approximately 4-fold by a ;dose of phenobarbital as low as 0.9 mg/kg. ;[1429..1442]:substance:"phenobarbital" ;[1444..1450]:quantitative-value:"0.9-75" ;[1452..1461]:quantitative-units:"mg/kg/day" ;[1504..1529]:substance:"aminopyrine-N-demethylase" ;[1557..1563]:quantitative-value:"2-fold" ;[1585..1587]:quantitative-value:"75" ;[1588..1597]:quantitative-units:"mg/kg/day" ;[1601..1630]:substance:"pentoxyresorufin O-dealkylase" ;[1666..1674]:quantitative-value:"140-fold" ;[1707..1713]:quantitative-value:"4-fold" ;[1727..1740]:substance:"phenobarbital" ;[1751..1754]:quantitative-value:"0.9" ;[1756..1761]:quantitative-units:"mg/kg" (SENT (S (NP-SBJ (NP (NN:[1346..1351] Assay)) (PP (IN:[1352..1354] of) (NP (NP (JJ:[1355..1362] hepatic) (NNS:[1363..1373] microsomes)) (PP (IN:[1374..1378] from) (NP (NP (NNS:[1380..1384] rats)) (SBAR (WHNP-3 (WDT:[1385..1390] which)) (S (NP-SBJ-3 (-NONE-:[1390..1390] *T*)) (VP (VBD:[1391..1395] were) (VP (VBN:[1396..1406] pretreated) (NP-3 (-NONE-:[1406..1406] *)) (PP (IN:[1407..1411] with) (NP (NP (VBG:[1412..1419] varying) (NNS:[1420..1425] doses)) (PP (IN:[1426..1428] of) (NP (NN:[1429..1442] phenobarbital))) (PRN (-LRB-:[1443..1444] -LRB-) (FRAG (NP (NP (QP (CD:[1444..1447] 0.9) (HYPH:[1447..1448] -) (CD:[1448..1450] 75)) (NN:[1452..1454] mg)) (PP (SYM:[1454..1455] /) (NP (NN:[1455..1457] kg))) (PP (SYM:[1457..1458] /) (NP (NN:[1458..1461] day)))) (,:[1461..1462] ,) (NP (CD:[1463..1467] four) (JJ:[1468..1470] ip) (NNS:[1471..1481] injections))) (-RRB-:[1481..1482] -RRB-))))))))))))) (VP (VBD:[1483..1492] indicated) (SBAR (IN:[1493..1497] that) (S (SBAR-ADV (IN:[1498..1503] while) (S (NP-SBJ-2 (NN:[1504..1529] aminopyrine-N-demethylase) (NN:[1531..1539] activity)) (VP (VBD:[1540..1543] was) (VP (VBN:[1544..1551] induced) (NP-2 (-NONE-:[1551..1551] *)) (ADVP-EXT (RB:[1552..1556] only) (CD:[1557..1558] 2) (HYPH:[1558..1559] -) (RB:[1559..1563] fold)) (PP (IN:[1564..1566] at) (NP (DT:[1567..1570] the) (JJ:[1571..1578] maximum) (NN:[1579..1583] dose) (PRN (-LRB-:[1584..1585] -LRB-) (NP (NP (CD:[1585..1587] 75) (NN:[1588..1590] mg)) (PP (SYM:[1590..1591] /) (NP (NN:[1591..1593] kg))) (PP (SYM:[1593..1594] /) (NP (NN:[1594..1597] day)))) (-RRB-:[1597..1598] -RRB-)))))))) (,:[1598..1599] ,) (NP-SBJ-1 (NN:[1601..1617] pentoxyresorufin) (NN:[1618..1630] O-dealkylase) (NN:[1631..1639] activity)) (VP (VBD:[1640..1643] was) (VP (VP (VBN:[1644..1651] induced) (NP-1 (-NONE-:[1651..1651] *)) (ADVP-EXT=5 (RB:[1652..1665] approximately) (CD:[1666..1669] 140) (HYPH:[1669..1670] -) (RB:[1670..1674] fold)) (PP=4 (IN:[1675..1677] at) (NP (DT:[1679..1683] this) (NN:[1684..1688] dose)))) (CC:[1689..1692] and) (VP (ADVP-EXT=5 (QP (RB:[1693..1706] approximately) (CD:[1707..1708] 4)) (HYPH:[1708..1709] -) (RB:[1709..1713] fold)) (PP (IN:[1714..1716] by) (NP (NP (DT:[1717..1718] a) (NN:[1719..1723] dose)) (PP (IN:[1724..1726] of) (NP (NN:[1727..1740] phenobarbital))) (PP (IN:[1741..1743] as) (ADJP (JJ:[1744..1747] low) (PP (IN:[1748..1750] as) (NP (NP (CD:[1751..1754] 0.9) (NN:[1756..1758] mg)) (PP (SYM:[1758..1759] /) (NP (NN:[1759..1761] kg))))))))) (PP=4 (-NONE-:[1761..1761] *NOT*)))))))) (.:[1761..1762] .))) ;section 8 Span:1766..1810 ;PMID: 3985627 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1766..1770] PMID) (::[1770..1771] :) (CD:[1772..1779] 3985627) (-LRB-:[1780..1781] -LSB-) (NNP:[1781..1787] PubMed) (HYPH:[1788..1789] -) (NN:[1790..1797] indexed) (IN:[1798..1801] for) (NNP:[1802..1809] MEDLINE) (-RRB-:[1809..1810] -RSB-)))