Sticeped Rat Liver S9

Mantsoe a bohlokoa: OECD 471, Oecd 47D 472, Teko ea Tebo 47, Oectoxicity, Teko ea Minicity, MINROCOME / HGPrt Assay, TK Assance Assay, TK Assance Assay, TK Assance Assay, TK Assance Assay, TK Assay

Sehlahisoa sa Iphase

Kenyelletso

Li-rat sebete s9ke karolo ea bohlokoa ha e lekolaKhanya ea lefutsoMonyetla oa lik'hemik'hale, haholo-holo ho Desicologet. E tloaetse ho kopantsoe le li-vitro listates, tse kangTeko ea AMS mmeliteko tsa liphetoho, ho lekola thepa ea bokhachane ea metsoako. Ka ho fana ka sistimi ea enzchrome p450 (cyp450), cyp450), cyp450), ho thusa ho tseba hore na lik'hemik'hale li ka ba teng.

Li-rat sebete s9

Sekepe sa sebete se bua ka poso - Mittochondria Sugnatant e fumanoeng ho tsoa ho Rate Liver ka mor'a letoto la mapolanka. Poleloana e reng "susumetsoa" e bua ka kalafo ea likhoto tse ntlafatsang tšebetso ea li-enzchrome p450 (cyp450 ea li-Xenobiotic tsa Xenobiotic.

Thepa e sa tloaelehang Rati e nang le S9 e na le li-enzyme tse fapaneng tse akanang le li-enzyme tse fapaneng ho karolo ea kelello. Sena se kenyelletsa li-enzyme tse kang monoko oa p450 monooxjekland, tse tsamaisang li-biotransfformation tsa bilione, ka ho etsa joalo li etsisa metabolism ea sebete.

Ts'ebetso ea Cyp450 le Ts'ebetso ea Metabolic

Lelapa la Cytochrome P450M (Cyzyme (Cywnme Sekhahla sa Ratice Liver

Likarohano tse ngata qalong li hanyetsana litlokotsela empa li ka ba chefo ka mor'a metabolism ka har'a sebete. Tsena pro - Metsipona (e hlokang ho kenya tšebetsong metabolic) le pro - Carcinogens (e batlang ho kenyelletsa ts'ebetso ea ts'ebetso ea SV. Ntle le pokello ea metabolic enzymes e kang cyp450, lintho tsena li ka bonahala li se kotsi ho liteko tsa methapo ea setso.

Ka ho eketsa li-ran sebeted S9 ho Vitro bafuputsi, bafuputsi ba ka lekola hore na ke bokae ka li-enzyme tsa cyp4u. Sena ke sa bohlokoa haholo ho meriana ka ho khetheha, e le metabolism ea li-cyp4on e leng li-enzyme tsa cyp450 ke mohato o sa sebetseng ho pharmacokinetics tsa lithethefatsi tse ngata.

Likopo tsa rat li-ran

1. 1. Teko ea AMS (OECD 471)

Teko ea Ames, e hlalositsoeng ka tataisoOECD 471, ke e 'ngoe ea tse lokileng Ho kenyelletsa ho pepesetsoa li-colons tsa sammonella ho bona hore na e kenyelletsa liphetoho tse bakang libaktheria ho khutlela ho histerina - Boemo bo ikemetseng.

Ho etsisa mokhoa oa batho oa metabolic, sebete sa rasen S9 o kenyelletsoa tsamaisong ea liteko. Leqheka la S9 le fana ka li-enzyme tse hlokahalang, ho kenyelletsa simp350, e ka koluoeng ho boloka bosholu ba DNA ea Bacterial DNA ea Bacterial DNA ea Bacterial DNA. Motsoako ona oa S9 o nang le tlhahlobo ea Ames o lumella tlhahlobo e felletseng ea bo-muticic ka ho etsisa likhoebo tse tobileng le tse nang le mechanic.

2. 2.Liteko tsa liphetoho (Teko ea Aarration Aberration, tlhahlobo ea mirocroulle, le tse ling li-vitro Reass)

Ntle le tlhahlobo ea Ames, liteko tsa liphetoho li tloaetse ho lekola bokhoni ba lik'hemik'hale. Liteko tsena li na le thuso e ngata ho lekola tšenyo e fapaneng ea liphatsa tsa lefutso, ho kenyeletsoa ka liphetoho tsa chromosomal, li-concontion tsa khanni le sebopeho sa microcorlei. Ratice Rat Liver S9 e sebelisoa ha ho etsoa litheolelo ka mabaka a latelang:

Teko ea Microcleous (OECD 487)

Teko ena e bona ho etsoa ha microchalei ka lisele, e leng mekhatlo e nyane le e nyane e nang le li-chromosomes kapa li-chromosos tse felletseng nakong ea karohano ea sele. The Teko ea MicrocleousO khona ho bona Clastogenic (chromosota - e robehile) le aneugnic (e amang litlamorao tsa chromosos. Li-ranti li sa rarolloang S9 li sebelisoa mona ho kenya ts'ebetsong boima ba sehlahisoa sa tlhahlobo-leseling Sekhethi sa S9 se ntlafatsa tšenyo ea tlhahlobo ka ho tsamaisa ts'ebetso ea metaboli e ka bang teng VIVO.

Teko ea ABrosomal Abraration (OECD 473)

Seteko sena se lekanya hore na ntho e ka baka tšenyo ea sebopeho sa chromosome ka ho thibela likheo, litsamaiso, likulo le mefuta e meng ea menahano. Joalo ka tlhahlobo ea microcleus,Teko ea Aber Aberratione ka sebelisoa le kapa ntle le ts'ebetso ea metabolic. Li-ranti tse susumetsang S6 li eketsoa tsamaisong ea liteko ho etsisa metabolic ka har'a sebete, e lumella tlhahlobo ea lintho tse ka 'nang tsa etsa joalo ka sebete sa metabolism.

Tafole 1. Mehopolo e bapisang ea liteko

Hprt / hgprt assay (OECD 476)

HoHPT / HGPrt Assays, litso tsa hamster ea China (cho kapa vs Kamora kalafo e khuts'oane le nako ea matsatsi a supileng, lisele li phephetsoa ka 6-thioguanine; Ke li-clounta tse nang le taolo ea ho lahleheloa ke hypoxane-gunine phosphoribosyltransferase. Ka ho bapisa boholo ba kolone ea likokoana-hloko ho sebetsana le maemo a mangata a ho fetola liphetoho nakong ea liphetoho

Tk Assays (OECD 490 & OECD 476)

TheTk Assay Emloys e kanna ea lisele tsa L5178y lisele tse bolaeang (OECD 490) kapa lisele tse (OECD 476) heterozzygous ntlong ea mohloa oa mohloa. Kamora ho pepesetsoa lik'hemik'hale ho hlahisa lik'hemik'hale, lisele li hlaphoheloa 'me li ngotsoe bohareng ba trifluorothymidine e bolaeang lisele tse khotsofetseng. Ho ba le li-hlobo tsa Tk⁻ tse fetang matsatsi a 10-14, ka lihlopha tse nyane tsa kolone hangata li bonts'a liphetoho tsa chroosomal le lipalesa tse kholo tse bonts'ang liphetoho tsa chroosomal. Joalo ka ho HPT / HGPrt Assay, Taolo e Sebetsaneng ea Khakatso ea Khampani ea Khatom ea khokahano ea li-mustoen

4. 4. Tlhahlobo ea kotsi ea kankere

Li-Rat tsa Ratile S9 li boetse li sebelisoa lithutong tse etselitsoeng ho lekola mofets'e - e baka li-dintho. Ka ho ngola mekhoa ea metabolic e etsahalang ka sebete sa motho, karoloana ea S9 e ka thusa ho khetholla litlokotsi tse ka etsang hore metabotolites e ka lebisa ho mofets'e.

Tlhahlobo e ntlafalitsoeng ea Ames

Ho latela tataiso ea morao-rao e fanoeng ke Agency ea Europe (EMA), tlhahlobo ea Americ e kanna ea se ke ea khona ho utloisisa Ka hona, tlhahlobo e ntlafalitsoeng ea AM ena e ntlafalitsoeng Teko e ntlafalitsoeng ea AM enanthed Amber e hlahisitsoeng ea ho eketsa ka lehaho ea li-hamster e sa tsoakolla Lits'ebeletso tsa rat le hamter dethesants Ka ho sebelisa ho sebelisa hamster ea hamsters sebete s9, tlhahlobo ena e ntlafalitsoeng e fana ka maikutlo a motho e ntle ea motho le ho eketsa ho tšepahala ha liphetho.

Sephetho

Ho thusa Rat ea Itloang S9 ho Teko e Tšoanang ea Teko ea Termote Ka ho fana ka sistimi ea ts'ebetso ea metabolic, e ntlafatsa bokhoni ba ho ba le tlhahlobo e kang ea liphetoho tse hlokang metabotoliction ea ho ba Genotolic. Likopo tsa tsona li bohlokoa bakeng sa ho netefatsa polokeho ea lithethefatsi tse ncha, lik'hemik'hale le lihlahisoa tsa bareki. Ka karolo ea eona ea ho tsamaisa metabolism ea motho ea sebete, Rati ea Staver ea S9 e ntse e le karolo ea bohlokoa ea tlhahlobo ea polokeho ea sejoale-joale le ho laola tlhahlobo ea ts'ireletso ea sejoale-joale.