;PMID: 1976059 ;source_file_1894.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..46] = [t:0..46] ;1)sentence:[e:52..175] = [t:52..175] ;2)sentence:[e:176..259] = [t:176..259] ;3)section:[e:263..296] = [t:263..296] ;4)section:[e:300..470] = [t:300..470] ;5)sentence:[e:474..630] = [t:474..630] ;6)sentence:[e:631..870] = [t:631..870] ;7)sentence:[e:871..1000] = [t:871..1000] ;8)sentence:[e:1001..1190] = [t:1001..1190] ;9)sentence:[e:1191..1346] = [t:1191..1346] ;10)sentence:[e:1347..1509] = [t:1347..1509] ;11)sentence:[e:1510..1746] = [t:1510..1746] ;12)sentence:[e:1747..1960] = [t:1747..1960] ;13)sentence:[e:1961..2144] = [t:1961..2144] ;14)section:[e:2148..2192] = [t:2148..2192] ;section 0 Span:0..46 ;Drug Metab Dispos. 1990 Jul-Aug;18(4):398-402. (SEC (FRAG (NNP:[0..4] Drug) (NNP:[5..10] Metab) (NNP:[11..17] Dispos) (.:[17..18] .) (CD:[19..23] 1990) (CC:[24..28] Jul-) (CD:[28..34] Aug;18) (-LRB-:[34..35] -LRB-) (CD:[35..36] 4) (-RRB-:[36..37] -RRB-) (,:[37..38] :) (CD:[38..40] 39) (CD:[40..45] 8-402) (.:[45..46] .))) ;sentence 1 Span:52..175 ;Tissue, species, and substrate concentration differences in the ;position-selective hydroxylation of N-nitrosodibutylamine. ;[73..82]:substance:"substrate" ;[153..174]:substance:"N-nitrosodibutylamine" (SENT (NP-HLN (NP (NP (NN:[52..58] Tissue) (NML-1 (-NONE-:[58..58] *P*))) (,:[58..59] ,) (NP (NNS:[60..67] species) (NML-1 (-NONE-:[67..67] *P*))) (,:[67..68] ,) (CC:[69..72] and) (NP (NML (NN:[73..82] substrate) (NN:[83..96] concentration)) (NML-1 (NNS:[97..108] differences)))) (PP-LOC (IN:[109..111] in) (NP (NP (DT:[112..115] the) (ADJP (NN:[117..125] position) (HYPH:[125..126] -) (JJ:[126..135] selective)) (NN:[136..149] hydroxylation)) (PP (IN:[150..152] of) (NP (NN:[153..174] N-nitrosodibutylamine))))) (.:[174..175] .))) ;sentence 2 Span:176..259 ;Relationship to the distribution of cytochrome P-450 isozymes 2 (IIB) and 5 ;(IVB). ;[213..240]:cyp450:"cytochrome P-450 isozymes 2" ;[213..238]...[251..252]:cyp450:"cytochrome P-450 isozymes"..."5" ;[242..245]:cyp450:"IIB" ;[254..257]:cyp450:"IVB" (SENT (NP-HLN (NP (NN:[176..188] Relationship)) (PP (TO:[189..191] to) (NP (NP (DT:[192..195] the) (NN:[197..209] distribution)) (PP (IN:[210..212] of) (NP (NP (NP (NML-1 (NN:[213..223] cytochrome) (NN:[224..229] P-450) (NNS:[230..238] isozymes)) (CD:[239..240] 2)) (NP (NN:[241..242] -LRB-) (NN:[242..245] IIB) (-RRB-:[245..246] -RRB-))) (CC:[247..250] and) (NP (NP (NML-1 (-NONE-:[250..250] *P*)) (CD:[251..252] 5)) (NP (-LRB-:[253..254] -LRB-) (NN:[254..257] IVB) (-RRB-:[257..258] -RRB-))))))) (.:[258..259] .))) ;section 3 Span:263..296 ;Schulze J, Richter E, Philpot RM. (SEC (FRAG (NNP:[263..270] Schulze) (NNP:[271..273] J,) (NNP:[274..281] Richter) (NNP:[282..283] E) (,:[283..284] ,) (NNP:[285..292] Philpot) (NNP:[293..295] RM) (.:[295..296] .))) ;section 4 Span:300..470 ;Laboratory of Cellular and Molecular Pharmacology, National Institute of ;Environmental Health Sciences, National Institutes of Health, Research ;Triangle Park, NC 27709. (SEC (FRAG (NN:[300..310] Laboratory) (IN:[311..313] of) (NNP:[314..322] Cellular) (CC:[323..326] and) (NNP:[327..336] Molecular) (NNP:[337..349] Pharmacology) (,:[349..350] ,) (NNP:[351..359] National) (NNP:[360..369] Institute) (IN:[370..372] of) (NNP:[374..387] Environmental) (NNP:[388..394] Health) (NNP:[395..403] Sciences) (,:[403..404] ,) (NNP:[405..413] National) (NNPS:[414..424] Institutes) (IN:[425..427] of) (NNP:[428..434] Health) (,:[434..435] ,) (NNP:[436..444] Research) (NNP:[445..453] Triangle) (NNP:[455..459] Park) (,:[459..460] ,) (NNP:[461..463] NC) (.:[464..469] 27709) (.:[469..470] .))) ;sentence 5 Span:474..630 ;The relative rates of 3- and 4-hydroxylation of N-nitrosodibutylamine in ;microsomal preparations depend upon species, tissue, and substrate ;concentration. ;[522..543]:substance:"N-nitrosodibutylamine" ;[605..614]:substance:"substrate" (SENT (S (NP-SBJ (NP (DT:[474..477] The) (JJ:[478..486] relative) (NNS:[487..492] rates)) (PP (IN:[493..495] of) (NP (NP (NP (CD:[496..497] 3) (HYPH:[497..498] -) (NML-1 (-NONE-:[498..498] *P*))) (CC:[499..502] and) (NP (CD:[503..504] 4) (HYPH:[504..505] -) (NML-1 (NN:[505..518] hydroxylation)))) (PP (IN:[519..521] of) (NP (NN:[522..543] N-nitrosodibutylamine))) (PP-LOC (IN:[544..546] in) (NP (JJ:[548..558] microsomal) (NNS:[559..571] preparations)))))) (VP (VBP:[572..578] depend) (PP-CLR (IN:[579..583] upon) (NP (NP (NNS:[584..591] species)) (,:[591..592] ,) (NP (NN:[593..599] tissue)) (,:[599..600] ,) (CC:[601..604] and) (NP (NN:[605..614] substrate) (NN:[616..629] concentration))))) (.:[629..630] .))) ;sentence 6 Span:631..870 ;With rabbits, at a substrate concentration of 200 microM, the two reactions ;differ by less than 30% in preparations from liver, lung, or intestine, ;whereas the ratio of 4- to 3-hydroxylation is 2.0 with bladder and only 0.4 ;with kidney. ;[650..659]:substance:"substrate" ;[677..680]:quantitative-value:"200" ;[681..687]:quantitative-units:"microM" ;[728..731]:quantitative-value:"30%" ;[827..830]:quantitative-value:"2.0" ;[854..857]:quantitative-value:"0.4" (SENT (S (PP (IN:[631..635] With) (NP (NNS:[636..643] rabbits))) (,:[643..644] ,) (PP (IN:[645..647] at) (NP (NP (DT:[648..649] a) (NN:[650..659] substrate) (NN:[660..673] concentration)) (PP (IN:[674..676] of) (NP (CD:[677..680] 200) (NN:[681..687] microM))))) (,:[687..688] ,) (NP-SBJ (DT:[689..692] the) (CD:[693..696] two) (NNS:[698..707] reactions)) (VP (VBP:[708..714] differ) (PP-EXT (IN:[715..717] by) (NP (QP (JJR:[718..722] less) (IN:[723..727] than) (CD:[728..730] 30)) (NN:[730..731] %))) (PP-LOC (IN:[732..734] in) (NP (NP (NNS:[735..747] preparations)) (PP (IN:[748..752] from) (NP (NN:[753..758] liver) (,:[758..759] ,) (NN:[760..764] lung) (,:[764..765] ,) (CC:[766..768] or) (NN:[770..779] intestine))))) (,:[779..780] ,) (SBAR-ADV (IN:[781..788] whereas) (S (NP-SBJ (NP (DT:[789..792] the) (NN:[793..798] ratio)) (PP (IN:[799..801] of) (NP (NP (CD:[802..803] 4) (HYPH:[803..804] -) (NML-4 (-NONE-:[804..804] *P*))) (TO:[805..807] to) (NP (CD:[808..809] 3) (HYPH:[809..810] -) (NML-4 (NN:[810..823] hydroxylation)))))) (VP (VP (VBZ:[824..826] is) (NP-PRD=2 (CD:[827..830] 2.0)) (PP=3 (IN:[831..835] with) (NP (NN:[836..843] bladder)))) (CC:[844..847] and) (VP (NP-PRD=2 (RB:[849..853] only) (CD:[854..857] 0.4)) (PP=3 (IN:[858..862] with) (NP (NN:[863..869] kidney)))))))) (.:[869..870] .))) ;sentence 7 Span:871..1000 ;As the substrate concentration is lowered, this ratio increases to a maximum ;of about 2.0 in hepatic and pulmonary preparations. ;[878..887]:substance:"substrate" ;[958..961]:quantitative-value:"2.0" (SENT (S (PP (IN:[871..873] As) (S-NOM (NP-SBJ-2 (DT:[874..877] the) (NN:[878..887] substrate) (NN:[888..901] concentration)) (VP (VBZ:[902..904] is) (VP (VBN:[905..912] lowered) (NP-2 (-NONE-:[912..912] *)))))) (,:[912..913] ,) (NP-SBJ (DT:[914..918] this) (NN:[919..924] ratio)) (VP (VBZ:[926..935] increases) (PP-CLR (TO:[936..938] to) (NP (NP (DT:[939..940] a) (NN:[941..948] maximum)) (PP (IN:[949..951] of) (NP (QP (RB:[952..957] about) (CD:[958..961] 2.0)))))) (PP-LOC (IN:[962..964] in) (NP (NP (JJ:[965..972] hepatic) (NML-1 (-NONE-:[972..972] *P*))) (CC:[973..976] and) (NP (JJ:[977..986] pulmonary) (NML-1 (NNS:[987..999] preparations)))))) (.:[999..1000] .))) ;sentence 8 Span:1001..1190 ;The sum of the rates of 3- and 4-hydroxylation of N-nitrosodibutylamine in ;microsomal preparations from untreated rabbits is highest in those from lung ;(about 2-fold greater than liver). ;[1052..1073]:substance:"N-nitrosodibutylamine" ;[1163..1169]:quantitative-value:"2-fold" (SENT (S (NP-SBJ (NP (DT:[1001..1004] The) (NN:[1006..1009] sum)) (PP (IN:[1010..1012] of) (NP (NP (DT:[1013..1016] the) (NNS:[1017..1022] rates)) (PP (IN:[1023..1025] of) (NP (NP (NP (CD:[1026..1027] 3) (HYPH:[1027..1028] -) (NML-1 (-NONE-:[1028..1028] *P*))) (CC:[1029..1032] and) (NP (CD:[1033..1034] 4) (HYPH:[1034..1035] -) (NML-1 (NN:[1035..1048] hydroxylation)))) (PP (IN:[1049..1051] of) (NP (NN:[1052..1073] N-nitrosodibutylamine))) (PP-LOC (IN:[1074..1076] in) (NP (NP (JJ:[1078..1088] microsomal) (NNS:[1089..1101] preparations)) (PP (IN:[1102..1106] from) (NP (JJ:[1107..1116] untreated) (NNS:[1117..1124] rabbits)))))))))) (VP (VBZ:[1125..1127] is) (ADJP-PRD (JJS:[1128..1135] highest)) (PP-LOC (IN:[1136..1138] in) (NP (NP (DT:[1139..1144] those)) (PP (IN:[1145..1149] from) (NP (NP (NN:[1150..1154] lung)) (PRN (-LRB-:[1156..1157] -LRB-) (ADJP (ADJP (ADVP (QP (RB:[1157..1162] about) (CD:[1163..1164] 2)) (HYPH:[1164..1165] -) (RB:[1165..1169] fold)) (JJR:[1170..1177] greater)) (PP (IN:[1178..1182] than) (NP (NN:[1183..1188] liver)))) (-RRB-:[1188..1189] -RRB-))))))) (.:[1189..1190] .))) ;sentence 9 Span:1191..1346 ;Following treatment of rabbits with phenobarbital, however, the highest rate ;is with hepatic microsomes (about 2-fold greater than pulmonary ;microsomes). ;[1228..1241]:substance:"phenobarbital" ;[1304..1318]:quantitative-value:"2-fold greater" (SENT (S (S-ADV (NP-SBJ (-NONE-:[1191..1191] *)) (VP (VBG:[1191..1200] Following) (NP (NP (NN:[1201..1210] treatment)) (PP (IN:[1211..1213] of) (NP (NNS:[1214..1221] rabbits))) (PP (IN:[1222..1226] with) (NP (NN:[1228..1241] phenobarbital)))))) (,:[1241..1242] ,) (ADVP (RB:[1243..1250] however)) (,:[1250..1251] ,) (NP-SBJ (DT:[1252..1255] the) (JJS:[1256..1263] highest) (NN:[1264..1268] rate)) (VP (VBZ:[1269..1271] is) (PP-PRD (IN:[1272..1276] with) (NP (JJ:[1277..1284] hepatic) (NNS:[1285..1295] microsomes))) (PRN (-LRB-:[1296..1297] -LRB-) (ADJP (ADJP (ADVP-EXT (QP (RB:[1297..1302] about) (CD:[1304..1305] 2)) (HYPH:[1305..1306] -) (RB:[1306..1310] fold)) (JJR:[1311..1318] greater)) (PP (IN:[1319..1323] than) (NP (JJ:[1324..1333] pulmonary) (NNS:[1334..1344] microsomes)))) (-RRB-:[1344..1345] -RRB-))) (.:[1345..1346] .))) ;sentence 10 Span:1347..1509 ;Antibodies to cytochrome P-450 isozymes 2 (IIB) and 5 (IVB) together inhibit ;greater than 90% of the microsomal 3- and 4-hydroxylation of ;N-nitrosodibutylamine. ;[1347..1357]:substance:"Antibodies" ;[1361..1389]:cyp450:"cytochrome P-450 isozymes 2" ;[1361..1387]...[1400..1401]:cyp450:"cytochrome P-450 isozymes"..."5" ;[1391..1394]:cyp450:"IIB" ;[1403..1406]:cyp450:"IVB" ;[1425..1441]:quantitative-value:"greater than 90%" ;[1487..1508]:substance:"N-nitrosodibutylamine" (SENT (S (NP-SBJ (NP (NNS:[1347..1357] Antibodies)) (PP (TO:[1358..1360] to) (NP (NP (NP (NML-3 (NML (NN:[1361..1371] cytochrome) (NN:[1372..1377] P-450)) (NNS:[1379..1387] isozymes)) (CD:[1388..1389] 2)) (NP (NN:[1390..1391] -LRB-) (NN:[1391..1394] IIB) (-RRB-:[1394..1395] -RRB-))) (CC:[1396..1399] and) (NP (NP (NML-3 (-NONE-:[1399..1399] *P*)) (CD:[1400..1401] 5)) (NP (-LRB-:[1402..1403] -LRB-) (NN:[1403..1406] IVB) (-RRB-:[1406..1407] -RRB-)))))) (ADVP (RB:[1408..1416] together)) (VP (VBP:[1417..1424] inhibit) (NP (NP (QP (JJR:[1425..1432] greater) (IN:[1433..1437] than) (CD:[1438..1440] 90)) (NN:[1440..1441] %)) (PP (IN:[1442..1444] of) (NP (NP (DT:[1445..1448] the) (NML (NML (ADJP-2 (JJ:[1449..1459] microsomal)) (CD:[1461..1462] 3) (HYPH:[1462..1463] -) (NML-1 (-NONE-:[1463..1463] *P*))) (CC:[1464..1467] and) (NML (ADJP-2 (-NONE-:[1467..1467] *P*)) (CD:[1468..1469] 4) (HYPH:[1469..1470] -) (NML-1 (NN:[1470..1483] hydroxylation))))) (PP (IN:[1484..1486] of) (NP (NN:[1487..1508] N-nitrosodibutylamine))))))) (.:[1508..1509] .))) ;sentence 11 Span:1510..1746 ;The ratio of 4- to 3-hydroxylation with antibodies to isozyme 2 present is ;the same (2.0) as that obtained with purified isozyme 5, and the ratio with ;antibodies to isozyme 5 present is the same (0.2) as that with purified ;isozyme 2. ;[1551..1561]:substance:"antibodies" ;[1565..1574]:cyp450:"isozyme 2" ;[1596..1599]:quantitative-value:"2.0" ;[1633..1642]:cyp450:"isozyme 5" ;[1663..1673]:substance:"antibodies" ;[1677..1686]:cyp450:"isozyme 5" ;[1709..1712]:quantitative-value:"0.2" ;[1736..1745]:cyp450:"isozyme 2" (SENT (S (S (NP-SBJ (NP (DT:[1510..1513] The) (NN:[1514..1519] ratio)) (PP (IN:[1520..1522] of) (NP (NP (CD:[1523..1524] 4) (HYPH:[1524..1525] -)) (PP (TO:[1526..1528] to) (NP (CD:[1530..1531] 3) (HYPH:[1531..1532] -) (NN:[1532..1545] hydroxylation))))) (PP (IN:[1546..1550] with) (NP (NP (NNS:[1551..1561] antibodies)) (PP (TO:[1562..1564] to) (NP (NP (NN:[1565..1572] isozyme) (CD:[1573..1574] 2)) (ADJP (JJ:[1575..1582] present))))))) (VP (VBZ:[1583..1585] is) (NP-PRD (NP (NP (DT:[1586..1589] the) (JJ:[1590..1594] same)) (PRN (-LRB-:[1595..1596] -LRB-) (NP (CD:[1596..1599] 2.0)) (-RRB-:[1599..1600] -RRB-))) (PP (IN:[1601..1603] as) (NP (NP-1 (DT:[1604..1608] that)) (VP (VBN:[1610..1618] obtained) (NP-1 (-NONE-:[1618..1618] *)) (PP (IN:[1619..1623] with) (NP (VBN:[1624..1632] purified) (NN:[1633..1640] isozyme) (CD:[1641..1642] 5))))))))) (,:[1642..1643] ,) (CC:[1644..1647] and) (S (NP-SBJ (NP (DT:[1648..1651] the) (NN:[1652..1657] ratio)) (PP (IN:[1658..1662] with) (NP (NP (NNS:[1663..1673] antibodies)) (PP (TO:[1674..1676] to) (NP (NP (NN:[1677..1684] isozyme) (CD:[1685..1686] 5)) (ADJP (JJ:[1688..1695] present))))))) (VP (VBZ:[1696..1698] is) (NP-PRD (NP (NP (DT:[1699..1702] the) (JJ:[1703..1707] same)) (PRN (-LRB-:[1708..1709] -LRB-) (NP (CD:[1709..1712] 0.2)) (-RRB-:[1712..1713] -RRB-))) (PP (IN:[1714..1716] as) (NP (NP (DT:[1717..1721] that)) (PP (IN:[1722..1726] with) (NP (VBN:[1727..1735] purified) (NN:[1736..1743] isozyme) (CD:[1744..1745] 2)))))))) (.:[1745..1746] .))) ;sentence 12 Span:1747..1960 ;The Km with isozyme 5 is less than 10 microM, whereas the Km with isozyme 2 ;is 55 microM, a difference that explains why position selectivity in ;microsomal incubations is dependent upon substrate concentration. ;[1751..1753]:quantitative-name:"Km" ;[1759..1768]:cyp450:"isozyme 5" ;[1773..1785]:quantitative-value:"less than 10" ;[1786..1792]:quantitative-units:"microM" ;[1806..1808]:quantitative-name:"Km" ;[1814..1823]:cyp450:"isozyme 2" ;[1827..1829]:quantitative-value:"55" ;[1830..1836]:quantitative-units:"microM" ;[1936..1945]:substance:"substrate" (SENT (S (NP-SBJ (NP (DT:[1747..1750] The) (NN:[1751..1753] Km)) (PP (IN:[1754..1758] with) (NP (NN:[1759..1766] isozyme) (CD:[1767..1768] 5)))) (VP (VBZ:[1770..1772] is) (NP-PRD (QP (JJR:[1773..1777] less) (IN:[1778..1782] than) (CD:[1783..1785] 10)) (NN:[1786..1792] microM)) (,:[1792..1793] ,) (SBAR-ADV (IN:[1794..1801] whereas) (S (NP-SBJ (NP (DT:[1802..1805] the) (NN:[1806..1808] Km)) (PP (IN:[1809..1813] with) (NP (NN:[1814..1821] isozyme) (CD:[1822..1823] 2)))) (VP (VBZ:[1824..1826] is) (NP-PRD (CD:[1827..1829] 55) (NN:[1830..1836] microM))))) (,:[1836..1837] ,) (NP-ADV (NP (DT:[1838..1839] a) (NN:[1840..1850] difference)) (SBAR (WHNP-1 (WDT:[1852..1856] that)) (S (NP-SBJ-1 (-NONE-:[1856..1856] *T*)) (VP (VBZ:[1857..1865] explains) (SBAR (WHADVP-2 (RB:[1866..1869] why)) (S (NP-SBJ (NP (NN:[1870..1878] position) (NN:[1879..1890] selectivity)) (PP-LOC (IN:[1891..1893] in) (NP (JJ:[1894..1904] microsomal) (NNS:[1905..1916] incubations)))) (VP (VBZ:[1917..1919] is) (ADJP-PRD (JJ:[1920..1929] dependent) (PP (IN:[1931..1935] upon) (NP (NN:[1936..1945] substrate) (NN:[1946..1959] concentration))) (ADVP-2 (-NONE-:[1959..1959] *T*))))))))))) (.:[1959..1960] .))) ;sentence 13 Span:1961..2144 ;Also, differences in the relative and absolute rates of hydroxylation among ;various tissues reflect differences in the contents of isozymes 2 and ;5.(ABSTRACT TRUNCATED AT 250 WORDS) ;[2094..2104]:cyp450:"isozymes 2" ;[2094..2102]...[2109..2110]:cyp450:"isozymes"..."5" (SENT (S (ADVP (RB:[1961..1965] Also)) (,:[1965..1966] ,) (NP-SBJ (NP (NNS:[1967..1978] differences)) (PP (IN:[1979..1981] in) (NP (NP (DT:[1982..1985] the) (NML (NML (JJ:[1986..1994] relative) (NML-2 (-NONE-:[1994..1994] *P*))) (CC:[1995..1998] and) (NML (JJ:[1999..2007] absolute) (NML-2 (NNS:[2009..2014] rates))))) (PP (IN:[2015..2017] of) (NP (NN:[2018..2031] hydroxylation))))) (PP (IN:[2032..2037] among) (NP (JJ:[2038..2045] various) (NNS:[2046..2053] tissues)))) (VP (VBP:[2054..2061] reflect) (NP (NP (NNS:[2062..2073] differences)) (PP (IN:[2074..2076] in) (NP (NP (DT:[2077..2080] the) (NNS:[2081..2089] contents)) (PP (IN:[2091..2093] of) (NP (NP (NML-1 (NNS:[2094..2102] isozymes)) (CD:[2103..2104] 2)) (CC:[2105..2108] and) (NP (NML-1 (-NONE-:[2108..2108] *P*)) (CD:[2109..2110] 5)))))))) (.:[2110..2111] .)) (FRAG (-LRB-:[2111..2112] -LRB-) (S (NP-SBJ (NN:[2112..2120] ABSTRACT)) (VP (VBN:[2121..2130] TRUNCATED) (PP-LOC (IN:[2131..2133] AT) (NP (CD:[2134..2137] 250) (NNS:[2138..2143] WORDS))))) (-RRB-:[2143..2144] -RRB-))) ;ERROR_Sentence has multiple Children (Sentence Error)[1961..2144]::S:FRAG: ;section 14 Span:2148..2192 ;PMID: 1976059 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2148..2152] PMID) (::[2152..2153] :) (CD:[2154..2161] 1976059) (-LRB-:[2162..2163] -LSB-) (NNP:[2163..2169] PubMed) (HYPH:[2170..2171] -) (NN:[2172..2179] indexed) (IN:[2180..2183] for) (NNP:[2184..2191] MEDLINE) (-RRB-:[2191..2192] -RSB-)))