Ese methylene blue itera kanseri? Ibimenyetso byo mu bushakashatsi ku burozi

Methylene blue yagaragaje ibimenyetso by’ibibyimba mu bushakashatsi bw’igihe kirekire ku nyamaswa kandi itanga ibisubizo byiza mu bizamini byinshi byo muri laboratwari bipima kwangirika kw’amakuru ndangasano. Ibyo byagaragaye bikwiye kwitabwaho. Ntibyerekana amahirwe nyayo y’uko umuntu azarwara kanseri nyuma yo guhura na yo mu buryo runaka.

Isuzuma rya IARC ryasohotse mu 2016 ryashyize methylene blue mu Itsinda rya 3, bivuze ko ubushobozi bwayo bwo gutera kanseri mu bantu butashoboye gushyirwa mu cyiciro. Itsinda ry’abahanga nta makuru ryari rifite ku kanseri mu bantu kandi ryasanze ibimenyetso byo mu nyamaswa bifite aho bigarukira. Itsinda rya 3 ntirisobanura ko byemejwe ko nta ngaruka ifite. Nanone, kuba hari icyagaragaye mu nyamaswa ntibihita bisobanura ko buri buryo umuntu ahura na yo bwemejwe ko butera kanseri.

Ibibazo bitatu bigomba gusubizwa ukwabyo

Carcinogenicity ireba ukwiyongera cyangwa gukura kw’ibibyimba. Ubushakashatsi bw’igihe kirekire ku nyamaswa bushobora kumenya imiterere y’ibibyimba nyuma yo guhura n’ikintu mu buryo bwasobanuwe. Genotoxicity ireba kwangirika kw’amakuru ndangasano cyangwa ibikorwa by’uturemangingo bifitanye isano na yo. Ikizamini cya mutation gitanga igisubizo cyiza kiba ikimenyetso cyo kwitondera, ariko ntikibara mu buryo butaziguye kanseri mu bantu. Ibyago ku muntu bireba amahirwe y’uko habaho ingaruka mbi mu buryo nyakuri bwo guhura n’ikintu.

Ibi bibazo bisaba ibipimo bitandukanye. Kubara mutations muri bagiteri, gusuzuma uturemangingo tw’amaraso y’imbeba no gusuzuma ibibyimba mu gihe cya necropsy si ibipimo bishobora gusimburana. Nanone, ubushakashatsi bw’ubuvuzi bwerekana ko ikintu cyangiza uturemangingo twa kanseri ntibugaragaza niba kugihura na cyo kenshi bishobora gutangiza ibibyimba mu ngirangingo nzima. Ikiganiro cyihariye kuri methylene blue mu bushakashatsi bwa kanseri gisuzuma ibivugwa ku ikoreshwa ryayo mu kuvura.

Kugereranya ubushakashatsi: uburyo nyakuri bwo guhura na yo igihe kirekire

Ubushakashatsi bw’ingenzi bwakoresheje methylene blue trihydrate, itangwa muri methylcellulose yo mu mazi ya 0.5% hakoreshejwe oral gavage, ni ukuvuga kuyitanga mu gipimo cyagenwe binyuze mu muyoboro ujya mu gifu. Buri tsinda ry’igipimo mu bushakashatsi bw’igihe kirekire ryari rigizwe n’inyamaswa 50 z’igitsina gabo na 50 z’igitsina gore muri buri bwoko. Yatangwaga iminsi itanu mu cyumweru mu gihe cy’imyaka ibiri, nk’uko bivugwa muri raporo y’ubushakashatsi ya Auerbach na bagenzi be.

Imbonerahamwe igumana imyanzuro ya NTP yihariye kuri buri bwoko. Ingano ni miligarama z’ikintu cyageragejwe kuri kilogarama y’uburemere bw’umubiri w’inyamaswa ku minsi cyatangwagaho, si ibyifuzo ku bantu. Inyamaswa zahawe igipimo cya zero zahawe vehicle.

Model	Dose groups, mg/kg	Route and duration	NTP conclusion and relevant finding
Imbeba z’igitsina gabo za F344/N	0, 5, 25, 50	Oral gavage; iminsi itanu/icyumweru; imyaka ibiri	Ibimenyetso bimwe: pancreatic islet-cell adenomas n’izamuka rya adenoma/carcinoma byahurijwe hamwe.
Imbeba z’igitsina gore za F344/N	0, 5, 25, 50	Gahunda imwe	Nta kimenyetso cy’ibikorwa bitera kanseri muri ibi bihe.
Imbeba z’igitsina gabo za B6C3F1	0, 2.5, 12.5, 25	Oral gavage; iminsi itanu/icyumweru; imyaka ibiri	Ibimenyetso bimwe: small-intestinal carcinoma n’izamuka rya adenoma/carcinoma byahurijwe hamwe. Malignant lymphoma na yo ishobora kuba yari ifitanye isano na byo.
Imbeba z’igitsina gore za B6C3F1	0, 2.5, 12.5, 25	Gahunda imwe	Ibimenyetso bitarafata umwanzuro: izamuka rito rya malignant lymphoma.

“Some evidence” ni icyiciro cya NTP cyerekana icyagaragaye neza mu igerageza ariko gifite imbaraga nke kurusha “clear evidence.” “Equivocal” isobanura icyagaragaye kitizewe neza. Ibi byiciro byerekana imbaraga z’ibimenyetso, si ijanisha ry’ibyago cyangwa urutonde rw’imbaraga ikintu gifite mu gutera kanseri.

Igisubizo cyo mu mbeba z’igitsina gabo nticyari izamuka rihoraho uko igipimo cyiyongeraga. Pancreatic islet adenoma cyangwa carcinoma byagaragaye muri 4/50 mu itsinda ry’igereranya no muri 9/50, 14/50 na 8/50 uko ibipimo byazamukaga. Inyandiko y’ubushakashatsi yasohotse ivuga ko statistical significance yabonetse ku gipimo cyo hagati gusa. Ibi bituma inkuru yoroshye y’izamuka rigororotse idahura n’ibyabonetse; ariko ntibyemeza ko igipimo cyo hejuru cyarinze inyamaswa. Adenoma ni ikibyimba kitari malignant, mu gihe carcinoma ari malignant. Igipimo cyahurije hamwe ibi byombi ntigikwiye gusobanurwa nk’aho buri kibyimba cyabazwe cyari kanseri.

Impamvu incamake zitandukanye zishobora kumvikana nk’izivuguruzanya

Amakuru agezweho yo kwandikira PROVAYBLUE avuga ibyagaragaye muri pancreas y’imbeba z’igitsina gabo ariko akavuga ko nta neoplastic findings zifitanye isano n’umuti zagaragaye mu mbeba. Inyandiko y’ubushakashatsi ivuga ko izamuka rya neoplastic findings mu mbeba ritari rifite statistical significance, ariko ikerekana ko hari positive trends. NTP ariko yahaye imbeba ibyiciro byerekanwe haruguru.

Isesengura rya IARC ku bushakashatsi bwo mu nyamaswa risobanura itandukaniro ry’ingenzi mu mibare: ibyagaragaye mu mara y’imbeba z’igitsina gabo byari bifite dose trends zifite statistical significance, ariko amatsinda yari yahawe ibipimo atandukanye ntiyari afite significance mu igereranya rya buri tsinda n’itsinda ry’igereranya. Gupima imiterere rusange ku bipimo byose bitandukanye no gupima buri tsinda ukwaryo. Abasomyi bakwiye kugumana inkomoko y’amakuru n’imvugo yayo aho kubyegeranya byose mu magambo ngo “imbeba zarwaye kanseri” cyangwa ngo “ubushakashatsi ku mbeba bwari negative.” Nta na kimwe gitanga igipimo cya kanseri cyapimwe mu bantu.

Kugereranya ubushakashatsi: ibipimo byo kwangirika kw’amakuru ndangasano

Igice cya genetic toxicology muri NTP Technical Report 540 gisobanura urundi ruhererekane rw’amagerageza. S9 ni uruvange rwo muri laboratwari rurimo enzymes zo mu mwijima rukoreshwa mu kwigana metabolic activation. Kuba S9 ihari ntibihindura ikizamini cy’uturemangingo ngo kibe ubushakashatsi bwo guhura n’ikintu mu mubiri wose.

Test system	Actual exposure conditions	Measured endpoint and result
Ibizamini bya mutation muri bagiteri, lot ya kabiri yageragejwe	Salmonella: 0.25–150 µg/plate; E. coli: 0.25–1,500 µg/plate; hamwe na rat-liver S9 cyangwa itarimo	Mutations ziyongereye mu moko yageragejwe.
Uturemangingo twa Chinese hamster ovary twakuwe tukarerwa muri laboratwari	Igerageza rya sister-chromatid exchange ryarimo 0.17–2.5 µg/mL nta S9, kugeza kuri 5 µg/mL hamwe na S9; igerageza rya chromosome-aberration ryakoresheje 4.7–22 µg/mL	Ibisubizo bya exchange na chromosome-aberration byari positive.
Imbeba z’igitsina gabo, igerageza ry’igihe gito	Single intraperitoneal injection: 25, 50 or 150 mg/kg; samples at 48 hours	Nta kwiyongera kwa micronucleated erythrocytes mu musokoro w’amagufwa cyangwa mu maraso.
Imbeba z’igitsina gabo n’iz’igitsina gore, igerageza risubirwamo	Oral gavage: 25, 50, 100 or 200 mg/kg; iminsi itanu/icyumweru mu gihe cy’amezi atatu	Nta kwiyongera kwa micronucleated erythrocytes zo mu maraso yo ku mpande z’umubiri.

Micronucleus ni akaremangingo gato k’inyongera gafite ibice bya nucleus gashobora kugaragaza gucika kwa chromosome cyangwa gutakara kwayo mu gihe cyo kugabanyikana kw’uturemangingo. Ikizamini cy’uturemangingo tw’amaraso gitanga igisubizo negative kuri icyo kibazo cyihariye muri utwo turemangingo twafashweho ingero. Ntigishobora gukuraho buri bwoko bwose bwo kwangirika kwa DNA muri buri rugingo. Ku rundi ruhande, ikizamini positive ku turemangingo twororejwe muri laboratwari ntikitubwira concentration ingirangingo z’umuntu zagezeho.

Amakuru yo kwandikira umuti na yo agaragaza iyi miterere rusange: ibizamini bya bagiteri n’uturemangingo twororejwe muri laboratwari byari positive, naho ibizamini bya micronucleus mu mbeba bikaba negative. Kuvuga methylene blue gusa ko ari “genotoxic” cyangwa “non-genotoxic” bikuraho amakuru y’ingenzi mu gusobanura ibisubizo.

Icyo ibi bisobanura ku muntu wahuye na yo

Ubu bushakashatsi ntibutanga validated cancer-safe daily threshold ku bantu. Kugabanya igipimo cy’imbeba hakoreshejwe body-weight factor ntibyakemura itandukaniro mu kwinjira mu mubiri, metabolism, uburyo bwo kuyitanga, inshuro umuntu ayihura na yo cyangwa igihe cyose cyo kuyihura na yo mu buzima. Byatanga gusa ingano yahinduwe mu mibare, si gihamya y’umutekano.

Igerageza rya gavage ry’imyaka ibiri n’ubuvuzi bugufi bwo mu mutsi bukurikiranwa n’abaganga bibaza ibibazo bitandukanye. Iryo tandukaniro ribuza guhindura imibare mu buryo butaziguye; ntirisiba ibyagaragaye mu nyamaswa. Isuzuma rifite akamaro ritangirira ku kintu nyacyo n’imiterere yacyo, ingano, uburyo bwo kugitanga, inshuro, igihe n’impamvu yo kugikoresha. “Ibitonyanga bike” ntibigaragaza concentration cyangwa volume yapimwe.

Niba methylene blue yaratanzwe kubera impamvu y’ubuvuzi, ibyagaragaye ku bibyimba byonyine ntibishobora kwemeza niba inyungu z’ubwo buvuzi zararushije ibyago byabwo. Niba hatekerezwa kuyikoresha kenshi ku bushake, ibyago bya kanseri by’igihe kirekire bitapimwe ntibikwiye gusobanurwa nka zero. Ibibazo bishobora kugaragara vuba kurushaho, harimo imikoranire n’indi miti n’ubushobozi bwo kugira haemolysis, bisobanurwa muri ingaruka mbi n’ibihe bituma idakwiye gukoreshwa.

Ku bindi bisobanuro, koresha isomero ry’ubushakashatsi kugira ngo utandukanye ubushakashatsi bwo mu bantu n’amagerageza yo mu nyamaswa no mu turemangingo. Ikibazo cy’ingenzi kuri buri nyandiko ni uburyo bwo guhura n’ikintu yagerageje n’igisubizo nyacyo yapimye.