;PMID: 8155716 ;source_file_1792.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..49] = [t:0..49] ;1)sentence:[e:55..156] = [t:55..156] ;2)section:[e:160..199] = [t:160..199] ;3)section:[e:203..321] = [t:203..321] ;4)sentence:[e:325..494] = [t:325..494] ;5)sentence:[e:495..631] = [t:495..631] ;6)sentence:[e:632..891] = [t:632..891] ;7)sentence:[e:892..1084] = [t:892..1084] ;8)sentence:[e:1085..1239] = [t:1085..1239] ;9)sentence:[e:1240..1471] = [t:1240..1471] ;10)sentence:[e:1472..1614] = [t:1472..1614] ;11)sentence:[e:1615..1882] = [t:1615..1882] ;12)sentence:[e:1884..2082] = [t:1884..2082] ;13)section:[e:2086..2130] = [t:2086..2130] ;section 0 Span:0..49 ;Biochim Biophys Acta. 1994 Apr 13;1205(2):325-35. (SEC (FRAG (NNP:[0..7] Biochim) (NNP:[8..15] Biophys) (NNP:[16..20] Acta) (.:[20..21] .) (CD:[22..26] 1994) (NNP:[27..30] Apr) (CD:[31..38] 13;1205) (-LRB-:[38..39] -LRB-) (CD:[39..40] 2) (-RRB-:[40..41] -RRB-) (::[41..42] :) (CD:[42..44] 32) (CD:[44..48] 5-35) (.:[48..49] .))) ;sentence 1 Span:55..156 ;Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s ;to different flavonoids. ;[55..62]:substance:"Isozyme" ;[103..107]:substance:"cDNA" ;[118..130]:cyp450:"CYP1A P-450s" ;[145..155]:substance:"flavonoids" (SENT (NP-HLN (NP (NP (ADJP (NN:[55..62] Isozyme) (HYPH:[62..63] -) (ADJP-1 (-NONE-:[63..63] *P*))) (NML-2 (-NONE-:[63..63] *P*))) (CC:[64..67] and) (NP (ADJP (NN:[68..75] species) (HYPH:[75..76] -) (ADJP-1 (JJ:[76..84] specific))) (NML-2 (NN:[85..99] susceptibility)))) (PP (IN:[100..102] of) (NP (ADJP (NN:[103..107] cDNA) (HYPH:[107..108] -) (VBN:[108..117] expressed)) (NN:[118..123] CYP1A) (NNS:[124..130] P-450s))) (PP (TO:[131..133] to) (NP (JJ:[135..144] different) (NNS:[145..155] flavonoids))) (.:[155..156] .))) ;section 2 Span:160..199 ;Tsyrlov IB, Mikhailenko VM, Gelboin HV. (SEC (FRAG (NNP:[160..167] Tsyrlov) (NNP:[168..170] IB) (,:[170..171] ,) (NNP:[172..183] Mikhailenko) (NNP:[184..186] VM) (,:[186..187] ,) (NNP:[188..195] Gelboin) (NNP:[196..198] HV) (.:[198..199] .))) ;section 3 Span:203..321 ;Laboratory of Molecular Carcinogenesis, National Cancer Institute, National ;Institutes of Health, Bethesda, MD 20892. (SEC (FRAG (NN:[203..213] Laboratory) (IN:[214..216] of) (NNP:[217..226] Molecular) (NNP:[227..241] Carcinogenesis) (,:[241..242] ,) (NNP:[243..251] National) (NNP:[252..258] Cancer) (NNP:[259..268] Institute) (,:[268..269] ,) (NNP:[270..278] National) (NNPS:[280..290] Institutes) (IN:[291..293] of) (NNP:[294..300] Health) (,:[300..301] ,) (NNP:[302..310] Bethesda) (,:[310..311] ,) (NNP:[312..314] MD) (CD:[315..320] 20892) (.:[320..321] .))) ;sentence 4 Span:325..494 ;The inhibitory and stimulatory effects of six flavonoids with distinct ;hydroxylation patterns on the recombinant and hepatic mouse and human CYP1A ;P-450s were studied. ;[371..381]:substance:"flavonoids" ;[467..480]:cyp450:"CYP1A P-450s" (SENT (S (NP-SBJ-4 (NP (DT:[325..328] The) (NML (NML (JJ:[329..339] inhibitory) (NML-3 (-NONE-:[339..339] *P*))) (CC:[340..343] and) (NML (JJ:[344..355] stimulatory) (NML-3 (NNS:[356..363] effects))))) (PP (IN:[364..366] of) (NP (NP (CD:[367..370] six) (NNS:[371..381] flavonoids)) (PP (IN:[382..386] with) (NP (JJ:[387..395] distinct) (NN:[397..410] hydroxylation) (NNS:[411..419] patterns))))) (PP (IN:[420..422] on) (NP (DT:[423..426] the) (NML (NML (ADJP-2 (JJ:[427..438] recombinant) (CC:[439..442] and) (JJ:[443..450] hepatic)) (NN:[451..456] mouse) (NML-1 (-NONE-:[456..456] *P*))) (CC:[457..460] and) (NML (ADJP-2 (-NONE-:[460..460] *P*)) (JJ:[461..466] human) (NML-1 (NN:[467..472] CYP1A) (NNS:[474..480] P-450s))))))) (VP (VBD:[481..485] were) (VP (VBN:[486..493] studied) (NP-4 (-NONE-:[493..493] *)))) (.:[493..494] .))) ;sentence 5 Span:495..631 ;cDNA-expressed mouse CYP1A1 and CYP1A2 differed in their sensitivity to both ;hydroxylated and nonhydroxylated flavonoids, respectively. ;[495..499]:substance:"cDNA" ;[516..522]:cyp450:"CYP1A1" ;[527..533]:cyp450:"CYP1A2" ;[606..616]:substance:"flavonoids" (SENT (S (NP-SBJ (NP (ADJP-3 (NN:[495..499] cDNA) (HYPH:[499..500] -) (VBN:[500..509] expressed)) (NML-2 (NN:[510..515] mouse)) (NN:[516..522] CYP1A1)) (CC:[523..526] and) (NP (ADJP-3 (-NONE-:[526..526] *P*)) (NML-2 (-NONE-:[526..526] *P*)) (NN:[527..533] CYP1A2))) (VP (VBD:[534..542] differed) (PP (IN:[543..545] in) (NP (NP (PRP$:[546..551] their) (NN:[553..564] sensitivity)) (PP (TO:[565..567] to) (NP (CC:[568..572] both) (NP (VBN:[573..585] hydroxylated) (NML-1 (-NONE-:[585..585] *P*))) (CC:[586..589] and) (NP (JJ:[590..605] nonhydroxylated) (NML-1 (NNS:[606..616] flavonoids))))))) (,:[616..617] ,) (ADVP (RB:[618..630] respectively))) (.:[630..631] .))) ;sentence 6 Span:632..891 ;A comparison between the mouse and human CYP1A2 revealed that ;alpha-naphthoflavone and flavone did not change the benzo[a]pyrene ;3-hydroxylation activity of human CYP1A2 but inhibited its 7-ethoxyresorufin ;and 7-methoxyresorufin O-dealkylation activities. ;[674..680]:cyp450:"CYP1A2" ;[695..715]:substance:"alpha-naphthoflavone" ;[721..728]:substance:"flavone" ;[748..762]:substance:"benzo[a]pyrene" ;[798..804]:cyp450:"CYP1A2" ;[823..840]:substance:"7-ethoxyresorufin" ;[845..863]:substance:"7-methoxyresorufin" (SENT (S (NP-SBJ (NP (DT:[632..633] A) (NN:[635..645] comparison)) (PP (IN:[646..653] between) (NP (DT:[654..657] the) (NML (NML (NN:[658..663] mouse) (NML-3 (-NONE-:[663..663] *P*))) (CC:[664..667] and) (NML (JJ:[668..673] human) (NML-3 (NN:[674..680] CYP1A2))))))) (VP (VBD:[681..689] revealed) (SBAR (IN:[690..694] that) (S (NP-SBJ (NN:[695..715] alpha-naphthoflavone) (CC:[717..720] and) (NN:[721..728] flavone)) (VP (VP (VBD:[729..732] did) (RB:[733..736] not) (VP (VB:[737..743] change) (NP (NP (DT:[744..747] the) (NML (NN:[748..762] benzo-LSB-a-RSB-pyrene) (NN:[763..778] 3-hydroxylation)) (NN:[779..787] activity)) (PP (IN:[788..790] of) (NP (JJ:[791..796] human) (NN:[798..804] CYP1A2)))))) (CC:[805..808] but) (VP (VBD:[809..818] inhibited) (NP (PRP$:[819..822] its) (NML (NML (NML (NN:[823..840] 7-ethoxyresorufin) (NML-1 (-NONE-:[840..840] *P*))) (NML-2 (-NONE-:[840..840] *P*))) (CC:[841..844] and) (NML (NML (NN:[845..863] 7-methoxyresorufin) (NML-1 (NN:[864..878] O-dealkylation))) (NML-2 (NNS:[880..890] activities)))))))))) (.:[890..891] .))) ;sentence 7 Span:892..1084 ;In contrast, hydroxylated flavonoids increased the 7-methoxyresorufin ;O-demethylation and acetanilide 4-hydroxylation activities of cDNA-expressed ;human CYP1A2 and in human liver microsomes. ;[918..928]:substance:"flavonoids" ;[944..962]:substance:"7-methoxyresorufin" ;[983..994]:substance:"acetanilide" ;[1026..1030]:substance:"cDNA" ;[1047..1053]:cyp450:"CYP1A2" (SENT (S (PP (IN:[892..894] In) (NP (NN:[895..903] contrast))) (,:[903..904] ,) (NP-SBJ (VBN:[905..917] hydroxylated) (NNS:[918..928] flavonoids)) (VP (VBD:[929..938] increased) (NP (NP (DT:[939..942] the) (NML (NML (NML (NN:[944..962] 7-methoxyresorufin) (NN:[963..978] O-demethylation)) (NML-1 (-NONE-:[978..978] *P*))) (CC:[979..982] and) (NML (NML (NN:[983..994] acetanilide) (NN:[995..1010] 4-hydroxylation)) (NML-1 (NNS:[1011..1021] activities))))) (PP (PP (IN:[1022..1024] of) (NP (ADJP (NN:[1026..1030] cDNA) (HYPH:[1030..1031] -) (VBN:[1031..1040] expressed)) (JJ:[1041..1046] human) (NN:[1047..1053] CYP1A2))) (CC:[1054..1057] and) (PP-LOC (IN:[1058..1060] in) (NP (JJ:[1061..1066] human) (NN:[1067..1072] liver) (NNS:[1073..1083] microsomes)))))) (.:[1083..1084] .))) ;sentence 8 Span:1085..1239 ;These compounds inhibited the benzo[a]pyrene 3-hydroxylase activity of ;cDNA-expressed CYP1A1 and CYP1A2s as well as in mouse and human liver ;microsomes. ;[1091..1100]:substance:"compounds" ;[1116..1144]:cyp450:"benzo[a]pyrene 3-hydroxylase" ;[1157..1161]:substance:"cDNA" ;[1172..1178]:cyp450:"CYP1A1" ;[1184..1191]:cyp450:"CYP1A2s" (SENT (S (NP-SBJ (DT:[1085..1090] These) (NNS:[1091..1100] compounds)) (VP (VBD:[1102..1111] inhibited) (NP (NP (DT:[1112..1115] the) (NML (NN:[1116..1130] benzo-LSB-a-RSB-pyrene) (NN:[1131..1144] 3-hydroxylase)) (NN:[1145..1153] activity)) (PP (PP (IN:[1154..1156] of) (NP (NP (ADJP-2 (NN:[1157..1161] cDNA) (HYPH:[1161..1162] -) (VBN:[1162..1171] expressed)) (NN:[1172..1178] CYP1A1)) (CC:[1179..1182] and) (NP (ADJP-2 (-NONE-:[1182..1182] *P*)) (NNS:[1184..1191] CYP1A2s)))) (CONJP (RB:[1192..1194] as) (RB:[1195..1199] well) (IN:[1200..1202] as)) (PP-LOC (IN:[1203..1205] in) (NP (NP (NN:[1206..1211] mouse) (NML-1 (-NONE-:[1211..1211] *P*))) (CC:[1212..1215] and) (NP (JJ:[1216..1221] human) (NML-1 (NN:[1222..1227] liver) (NNS:[1228..1238] microsomes)))))))) (.:[1238..1239] .))) ;sentence 9 Span:1240..1471 ;Hydroxylated flavonoids did not inhibit NADPH-cytochrome P-450 ;oxidoreductase activity but inhibited NADPH-2,6-dichlorophenolindophenol ;oxidoreductase activity in liver microsomes and in microsomes from ;recombinant Hep G2 cells. ;[1253..1263]:substance:"flavonoids" ;[1281..1318]:substance:"NADPH-cytochrome P-450 oxidoreductase" ;[1343..1392]:substance:"NADPH-2,6-dichlorophenolindophenol oxidoreductase" (SENT (S (NP-SBJ (VBN:[1240..1252] Hydroxylated) (NNS:[1253..1263] flavonoids)) (VP (VP (VBD:[1265..1268] did) (RB:[1269..1272] not) (VP (VB:[1273..1280] inhibit) (NP (NML (NML (NML (NN:[1281..1286] NADPH)) (HYPH:[1286..1287] -) (NML (NN:[1287..1297] cytochrome) (NN:[1298..1303] P-450))) (NN:[1304..1318] oxidoreductase)) (NN:[1319..1327] activity)))) (CC:[1328..1331] but) (VP (VBD:[1332..1341] inhibited) (NP (NML (NN:[1343..1377] NADPH-2,6-dichlorophenolindophenol) (NN:[1378..1392] oxidoreductase)) (NN:[1393..1401] activity)) (PP-LOC (PP (IN:[1402..1404] in) (NP (NN:[1405..1410] liver) (NNS:[1411..1421] microsomes))) (CC:[1423..1426] and) (PP (IN:[1427..1429] in) (NP (NP (NNS:[1430..1440] microsomes)) (PP (IN:[1441..1445] from) (NP (JJ:[1446..1457] recombinant) (NN:[1458..1461] Hep) (NN:[1462..1464] G2) (NNS:[1465..1470] cells)))))))) (.:[1470..1471] .))) ;sentence 10 Span:1472..1614 ;Structure-activity relationships indicated the importance of hydroxyl groups ;in the 5- and 7-positions on the A ring of the flavane nucleus. ;[1598..1605]:substance:"flavane" (SENT (S (NP-SBJ (NP (NN:[1472..1481] Structure) (HYPH:[1481..1482] -) (NN:[1482..1490] activity)) (NNS:[1492..1505] relationships)) (VP (VBD:[1506..1515] indicated) (NP (NP (DT:[1516..1519] the) (NN:[1520..1530] importance)) (PP (IN:[1531..1533] of) (NP (NN:[1534..1542] hydroxyl) (NNS:[1543..1549] groups)))) (PP-LOC (IN:[1550..1552] in) (NP (NP (DT:[1553..1556] the) (NML (NML (CD:[1557..1558] 5) (HYPH:[1558..1559] -) (NML-1 (-NONE-:[1559..1559] *P*))) (CC:[1560..1563] and) (NML (CD:[1565..1566] 7) (HYPH:[1566..1567] -) (NML-1 (NNS:[1567..1576] positions))))) (PP-LOC (IN:[1577..1579] on) (NP (NP (DT:[1580..1583] the) (NN:[1584..1585] A) (NN:[1586..1590] ring)) (PP (IN:[1591..1593] of) (NP (DT:[1594..1597] the) (NN:[1598..1605] flavane) (NN:[1606..1613] nucleus)))))))) (.:[1613..1614] .))) ;sentence 11 Span:1615..1882 ;These hydroxyl groups accounted for the inhibitory potency of chrysin on ;each of the activities of the expressed P-450s, while presence of a hydroxyl ;group at the 4'-position on the B ring decreased the inhibitory potency of ;naringenin compared to that of chrysin. ;[1678..1685]:substance:"chrysin" ;[1730..1736]:cyp450:"P-450s" ;[1843..1853]:substance:"naringenin" ;[1874..1881]:substance:"chrysin" (SENT (S (NP-SBJ (DT:[1615..1620] These) (NN:[1621..1629] hydroxyl) (NNS:[1630..1636] groups)) (VP (VBD:[1638..1647] accounted) (PP-CLR (IN:[1648..1651] for) (NP (NP (DT:[1652..1655] the) (JJ:[1656..1666] inhibitory) (NN:[1667..1674] potency)) (PP (IN:[1675..1677] of) (NP (NN:[1678..1685] chrysin))) (PP (IN:[1686..1688] on) (NP (NP (DT:[1689..1693] each)) (PP (IN:[1694..1696] of) (NP (NP (DT:[1697..1700] the) (NNS:[1701..1711] activities)) (PP (IN:[1712..1714] of) (NP (DT:[1715..1718] the) (VBN:[1720..1729] expressed) (NNS:[1730..1736] P-450s))))))))) (,:[1736..1737] ,) (SBAR-ADV (IN:[1738..1743] while) (S (NP-SBJ (NP (NN:[1744..1752] presence)) (PP (IN:[1753..1755] of) (NP (NP (DT:[1756..1757] a) (NN:[1758..1766] hydroxyl) (NN:[1767..1772] group)) (PP-LOC (IN:[1773..1775] at) (NP (NP (DT:[1776..1779] the) (NML (CD:[1780..1781] 4) (SYM:[1781..1782] ')) (HYPH:[1782..1783] -) (NN:[1783..1791] position)) (PP-LOC (IN:[1792..1794] on) (NP (DT:[1795..1798] the) (NN:[1799..1800] B) (NN:[1802..1806] ring)))))))) (VP (VBD:[1807..1816] decreased) (NP (NP (DT:[1817..1820] the) (JJ:[1821..1831] inhibitory) (NN:[1832..1839] potency)) (PP (IN:[1840..1842] of) (NP (NN:[1843..1853] naringenin)))) (S-ADV (NP-SBJ (-NONE-:[1853..1853] *)) (VP (VBN:[1854..1862] compared) (NP (-NONE-:[1862..1862] *)) (PP-CLR (TO:[1863..1865] to) (NP (NP (DT:[1866..1870] that)) (PP (IN:[1871..1873] of) (NP (NN:[1874..1881] chrysin))))))))))) (.:[1881..1882] .))) ;sentence 12 Span:1884..2082 ;The ortho-orientation of a hydroxyl group on the B ring was of importance, ;inasmuch as quercetin was more potent than morin as an inhibitor of ;cDNA-expressed and hepatic microsomal monooxygenases. ;[1972..1981]:substance:"quercetin" ;[2003..2008]:substance:"morin" ;[2015..2024]:substance:"inhibitor" ;[2029..2033]:substance:"cDNA" ;[2067..2081]:substance:"monooxygenases" (SENT (S (NP-SBJ (NP (DT:[1884..1887] The) (AFX:[1888..1893] ortho) (HYPH:[1893..1894] -) (NN:[1894..1905] orientation)) (PP (IN:[1906..1908] of) (NP (NP (DT:[1909..1910] a) (NN:[1911..1919] hydroxyl) (NN:[1920..1925] group)) (PP-LOC (IN:[1926..1928] on) (NP (DT:[1929..1932] the) (NN:[1933..1934] B) (NN:[1935..1939] ring)))))) (VP (VBD:[1940..1943] was) (PP-PRD (IN:[1944..1946] of) (NP (NN:[1947..1957] importance))) (,:[1957..1958] ,) (SBAR-ADV (RB:[1960..1968] inasmuch) (IN:[1969..1971] as) (S (NP-SBJ (NN:[1972..1981] quercetin)) (VP (VBD:[1982..1985] was) (ADJP-PRD (ADJP (RBR:[1986..1990] more) (JJ:[1991..1997] potent)) (PP (IN:[1998..2002] than) (NP (NN:[2003..2008] morin)))) (PP (IN:[2009..2011] as) (NP (NP (DT:[2012..2014] an) (NN:[2015..2024] inhibitor)) (PP (IN:[2025..2027] of) (NP (NP (ADJP (NN:[2029..2033] cDNA) (HYPH:[2033..2034] -) (VBN:[2034..2043] expressed)) (NML-1 (-NONE-:[2043..2043] *P*))) (CC:[2044..2047] and) (NP (JJ:[2048..2055] hepatic) (NML-1 (JJ:[2056..2066] microsomal) (NNS:[2067..2081] monooxygenases))))))))))) (.:[2081..2082] .))) ;section 13 Span:2086..2130 ;PMID: 8155716 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2086..2090] PMID) (::[2090..2091] :) (CD:[2092..2099] 8155716) (NN:[2100..2101] -LSB-) (NNP:[2101..2107] PubMed) (::[2108..2109] -) (NN:[2110..2117] indexed) (IN:[2118..2121] for) (NNP:[2122..2130] MEDLINE-RSB-)))