oxidative metabolism of chlopromazine (cpz) in 3t3 cells

2
Sensory raspwamry initalian of Cerhfllcluene we5 studied in BalblC male mice usmg the plethvsmegraphu merhoo. Ice concentration which decreased the respira,ory rate I,? 50% (RD50 value1 ‘.~a5 deter- mined to be 857 ppm (56bt 139 ppm for 95% confidence limits). To study inhalation toxicity, male and lemals outbred Wistar rats were 8%. posed in dynamic inhale,& chambers lo vapors of &ethyltcluene in conce”,rat,ans at 1130 and 500 ppm. 6 hours/day. 5 dayshwek for 4 weeks. NC significant changes were observed in water apd food cow sumplion and bcdywrghtgsln. SteliStiCallye~gnlfiean,.ccncenrretion- dependen, changes in tc7al cell numbere and macrophage end grew ulocyte numbers were found in bronchoalveolar lavage IBAU In BAL superne,ant a signdicant. ccncen,reticn+?la,ed increase in tctal pm- tan, LDH. yqlutamvl,ransferase. pglucuronidase, acid phosphatase and muccprcteins was ncted l11etopalhobgy revealed an increased rate of bronchitis and pneumonia in male rate exposed 10 500 ppm of 4-elhvlloluene. No signiiicant cha?zr? were observed I” rewraiory tract and BAL of female r& expcsed :o ~ethylotoluene Keywcrbs’ Qelhylc4aluene: organic s.akents: inhalaion,orici,y; brcn- ehoalwlar lavage IBALI: eew-orv irrltatian is no evidence oiindfpendent yenctc& of this age”,. For a betier undsrsta~~ding of the acliw of rhe drug wetesled ,he possible mute- genie or clastogenic effect ot pan,cx~fyUine OR human peripheral &?- ohocvles m \i,rc. The number of abemnt cells increased in a do- bepehdsnt manner. A delailed analysis of chromoscmal aberrations shows ,hat chramacd type of abervaons prevaled. The experiment showed that pentc#ltVlline has a claslcgenic effen in this testing ws- tern. The resulls confirm cur previous obsewatlons of a clastogenic effect of lh~s drug in Y 79 ceils. which is pmbaMy CcnsisP of lhe inhi. bnicn cf a new repliccn initialian and DNA chain elongation. 11,sl~mcnwd 0 .?I 111. MlMllD” “I1I.322.275,ww ;$words: pentoxifylline: human peripheral lymphacyles: mutsgenic- Human Alak Due to Mercury In Paad -Twenty Yews tidy in Poland 1. Szpreng~er-Ju5zkiewicr. De~amnen:clPhamMcc/o~and l-icolcgK National Velwmery Innirure Pufaw Poland Summary ~lall~t!c~ of data Irom random sampling studies conducted durq ,97&1990 in Polish laboratories. investfgating :he presence 01 mercury in food, ars presented. Over 16 thousand results obrained by meanscf atomic rbscrptwn spectrcphotomelrywere c&&d. Mean ccnccs:raiicns 1016 kinds of Iwd o, animal and plan, originwere cal- ctdared.Theccmpar~sonofmercunlbvelsin,waccnsecut~vadecades indicates a certain uend of decreasing ifi mercuw concentration in food Based on the results obtained for Ihe Ian decade m ,hlS sludy. dietary imdke cf mercury m Pcland was calculated. Keywords: mercury: ccnlamma,~on: food; dietary Intake; risk ewess. men, cc, affected by the combin&,. The ukeroge;ic &ec, cl the combi- nat~cn was not significantb increased. Aspirin abne decreased lIpid percxideticn and OEX increased aniline hvdrcwlaseactivitv. The ccm- bin&n signilicenlly increased cyiochrome P-450 cocten,. E,hflmcr- phine Ndemelhylase and aniline hydmxylase activities, cylachmme b-5 and lipid pemxidation were not effec,ed by the combination. The analgesic effect increased significantly a!,er single or muhiple I4 da-s) xlminietra,ianof thecombination The ~lationshipbetwesnthehlgher ssplrin loxsin/. the icxcased analgaic elfem and ,he changes in bib chemical paramelhen were discussed Kqwcrds: aspirin: dexacwthascne; toxicity: monooxqgena~e8: cy_ tochrome P-450 lblwanmto IPPN4nducad ~klnwlr In DlWsllc Rata M.Tariq. S. Al Deeb. K. AI Mctiair”, H A Khan. Neuroscience Research rimu~. Armed Forces HovitaL W 9 r2.6?0. Box 78.97. fliuadh, Saudi Arabia Chronic adminie,radcnti p.fl lmincdiprcpioni,rileiIDPN~. a neurctcxin ,D rats pmduces a persistent behavioral sycdmme characterized by certain dyskinetic movements. 1llPN+,duced dpkinesia has been et. tnbuied to abncrmalilies in neur~lrensminar splem including activa- devaopeddyskinesia on 12th day of shady. The ssverih’ d dy&inesii in diabetic rats was also signlcamly less as compared ,c IDPN only treated rats. The treatment of animals with insulin attenuated diabetes lndrrced delay of 1DPN d@kinesia. Suppcrred by Research tr Ethical Committee. AKW. Saudi Arabia. Cwlaib~ AaWaolitm of Chlopromcalne (CPZ) In 3T3 J.M. Thorndike. V. Awhcnvpiltai. MN. Moore,, PH. Bach. Swiss rnousa 3T3fibroblasrs are pariicularlv sensilive IlCec = 10 rhll to CPZ 111Ouan,~tst~vas,mc,ure ec,wi,vrele,icn~h~~ data wasdewed from CPZ analogbee and metabolites u;mg Ihe Uli assay 121 Lo mea surs nabilitv. N.Ndimethvl-prawnamine substhuted tricvclics with an unoxidised 6.7.5. Bring or a 6.9 or 7. Ed~hydtcxysubsli,uUcn were cflotcxic 7.BD~hydmxy.CPZ was ,he rnc~t cytotox~c compound IIC, < P pM). Anticxlddnls prctezted cells expcaed M the I& of CPZ. II- Tcccpheml110 rrM1 increased cells survival by 30%. L-axcrbic acid (10 )I,‘.,) and glu,a,h,ons 110 PM, by 1%20%. but oni~ L.aworb,e a&d

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Page 1: Oxidative Metabolism of Chlopromazine (CPZ) in 3T3 Cells

Sensory raspwamry initalian of Cerhfllcluene we5 studied in BalblC male mice usmg the plethvsmegraphu merhoo. Ice concentration which decreased the respira,ory rate I,? 50% (RD50 value1 ‘.~a5 deter- mined to be 857 ppm (56bt 139 ppm for 95% confidence limits). To study inhalation toxicity, male and lemals outbred Wistar rats were 8%. posed in dynamic inhale,& chambers lo vapors of &ethyltcluene in conce”,rat,ans at 1130 and 500 ppm. 6 hours/day. 5 dayshwek for 4 weeks. NC significant changes were observed in water apd food cow sumplion and bcdywrghtgsln. SteliStiCallye~gnlfiean,.ccncenrretion- dependen, changes in tc7al cell numbere and macrophage end grew ulocyte numbers were found in bronchoalveolar lavage IBAU In BAL superne,ant a signdicant. ccncen,reticn+?la,ed increase in tctal pm- tan, LDH. yqlutamvl,ransferase. pglucuronidase, acid phosphatase and muccprcteins was ncted l11etopalhobgy revealed an increased rate of bronchitis and pneumonia in male rate exposed 10 500 ppm of 4-elhvlloluene. No signiiicant cha?zr? were observed I” rewraiory tract and BAL of female r& expcsed :o ~ethylotoluene

Keywcrbs’ Qelhylc4aluene: organic s.akents: inhalaion,orici,y; brcn- ehoalwlar lavage IBALI: eew-orv irrltatian

is no evidence oiindfpendent yenctc& of this age”,. For a betier undsrsta~~ding of the acliw of rhe drug wetesled ,he possible mute- genie or clastogenic effect ot pan,cx~fyUine OR human peripheral &?- ohocvles m \i,rc. The number of abemnt cells increased in a do- bepehdsnt manner. A delailed analysis of chromoscmal aberrations shows ,hat chramacd type of abervaons prevaled. The experiment showed that pentc#ltVlline has a claslcgenic effen in this testing ws- tern. The resulls confirm cur previous obsewatlons of a clastogenic effect of lh~s drug in Y 79 ceils. which is pmbaMy CcnsisP of lhe inhi. bnicn cf a new repliccn initialian and DNA chain elongation.

11, sl~mcnwd 0 .?I 111. MlMllD” “I1I.322.275,ww

;$words: pentoxifylline: human peripheral lymphacyles: mutsgenic-

Human Alak Due to Mercury In Paad -Twenty Yews tidy in Poland 1. Szpreng~er-Ju5zkiewicr. De~amnen:clPhamMcc/o~and l-icolcgK National Velwmery Innirure Pufaw Poland

Summary ~lall~t!c~ of data Irom random sampling studies conducted durq ,97&1990 in Polish laboratories. investfgating :he presence 01 mercury in food, ars presented. Over 16 thousand results obrained by meanscf atomic rbscrptwn spectrcphotomelrywere c&&d. Mean ccnccs:raiicns 10 16 kinds of Iwd o, animal and plan, originwere cal- ctdared.Theccmpar~sonofmercunlbvelsin,waccnsecut~vadecades indicates a certain uend of decreasing ifi mercuw concentration in food Based on the results obtained for Ihe Ian decade m ,hlS sludy. dietary imdke cf mercury m Pcland was calculated.

Keywords: mercury: ccnlamma,~on: food; dietary Intake; risk ewess. men,

cc, affected by the combin&,. The ukeroge;ic &ec, cl the combi- nat~cn was not significantb increased. Aspirin abne decreased lIpid percxideticn and OEX increased aniline hvdrcwlaseactivitv. The ccm- bin&n signilicenlly increased cyiochrome P-450 cocten,. E,hflmcr- phine Ndemelhylase and aniline hydmxylase activities, cylachmme b-5 and lipid pemxidation were not effec,ed by the combination. The analgesic effect increased significantly a!,er single or muhiple I4 da-s) xlminietra,ianof thecombination The ~lationshipbetwesnthehlgher ssplrin loxsin/. the icxcased analgaic elfem and ,he changes in bib chemical paramelhen were discussed

Kqwcrds: aspirin: dexacwthascne; toxicity: monooxqgena~e8: cy_ tochrome P-450

lblwanmto IPPN4nducad ~klnwlr In DlWsllc Rata

M.Tariq. S. Al Deeb. K. AI Mctiair”, H A Khan. Neuroscience Research rimu~. Armed Forces HovitaL W 9 r2.6?0. Box 78.97. fliuadh, Saudi Arabia

Chronic adminie,radcnti p.fl lmincdiprcpioni,rileiIDPN~. a neurctcxin ,D rats pmduces a persistent behavioral sycdmme characterized by certain dyskinetic movements. 1llPN+,duced dpkinesia has been et. tnbuied to abncrmalilies in neur~lrensminar splem including activa-

devaopeddyskinesia on 12th day of shady. The ssverih’ d dy&inesii in diabetic rats was also signlcamly less as compared ,c IDPN only treated rats. The treatment of animals with insulin attenuated diabetes lndrrced delay of 1DPN d@kinesia.

Suppcrred by Research tr Ethical Committee. AKW. Saudi Arabia.

Cwlaib~ AaWaolitm of Chlopromcalne (CPZ) In 3T3

J.M. Thorndike. V. Awhcnvpiltai. MN. Moore,, PH. Bach.

Swiss rnousa 3T3fibroblasrs are pariicularlv sensilive IlCec = 10 rhll to CPZ 111 Ouan,~tst~vas,mc,ure ec,wi,vrele,icn~h~~ data wasdewed from CPZ analogbee and metabolites u;mg Ihe Uli assay 121 Lo mea surs nabilitv. N.Ndimethvl-prawnamine substhuted tricvclics with an unoxidised 6.7.5. Bring or a 6.9 or 7. Ed~hydtcxysubsli,uUcn were cflotcxic 7.BD~hydmxy.CPZ was ,he rnc~t cytotox~c compound IIC, < P pM). Anticxlddnls prctezted cells expcaed M the I& of CPZ. II- Tcccpheml110 rrM1 increased cells survival by 30%. L-axcrbic acid (10 )I,‘.,) and glu,a,h,ons 110 PM, by 1%20%. but oni~ L.aworb,e a&d

Page 2: Oxidative Metabolism of Chlopromazine (CPZ) in 3T3 Cells

pups. 35 per cent al pups of the lugher dose group’died during ,he first days after birth. In the prenatal treated pupswe~ght and cellularity

dB inter&v during 1.5.2 or 3 months 15 bows daC; and broad band 40_12MWHrunderS0,9oort00d8in(8nsltyduriinths 4 hours da~lylactes by analogy. Data must be isken in,0 cans~deratlan to evaluate the mumgenes due to anwoumensl iaclors