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An analysis of the effects of conjugation on the teratogenicity of aromatic amines in vitro
129 PORPBYRINGGENESISAND ENZYMEINDUCTION FROMPCB IN NAN:
MARONI, M.,
COLOMBI, A.,
FERIOLI, A.,
A DOSE-RESPONSE STUDY
AND FOA’, V.
XNSTITUTg FOR OCCUPATIONALHEALTH - UNIVERSITY OF MILAN (ITALY). 20122 MILANO, Urinery
VIA S.
BARNABA8
excretion
of D-glucaric acid @LA) and porphyrins from 8 to 4 carboxylic were measured in 51 PCB workers to determlne whether they were associated with the blood total PC6 concentrations in the workers and whether any aeeociation could be established among theee parameters. Mran GGT activity (27.8 U/L) and urinary GLA (71.7smolA.)and total porphyrin (93A sg/L) excretion were all increased when compared to reference values. Rlcod total PCB concentration, determined by packed column CLC, ranged from 88 to 1359 ppb I’nr the 28 workere for whom this meaeurement wae available. To achieve a normal dfstributlon, all the variables were transformed into log, velucs. No sinniftcant association was found either between GLA end GCT or single and total porphyrin homologues and the blood PCB concentration, A poeitive eaeociation (r=0,46g, PzO.01) was observed between individual valuea of GGT and GLA, Urinary GLA excretion poeitively correlated with f-COOH porphyrin excretion (r-0.416, P
gruupe and aerum GGT activity
#j ANALYSIS OF THE EFFECTS OF CONJUGATIONON THE T~RATOG~N~C~TY OF ANDNATiCAMfNES
IN
VITRO. FAUSTMAN-WATTS,E,T, GREENAWAY,J.C.2, WALKER, 5.2, FANTEL, A.G.2, JUCHAU, H.R.l.
DEPARTMENTSOF PHARMACOLOGY1AND PEDIATRICS2SCHOOL OF MEDICIINE, LMIVEHSITYDF WASHINGTON,SEATTLE,WA 98195
The objectiveof this study w&s to initiatean ex~tnin~t~on of the effect of conjugation on the terstogenicity-in vitro of 2=scetylsminofluorene metabolites. Sprtiuuu-Hawley rat embryoswere explantedon day 10 and cultured for 24 hours. Dur previouswork has shown thst when either N-~dro~=2~~etyl8m~nofluor~ne (N-OW-AAF)or N=aceto~=2=d~@tyl= aminofluorene(AAF) were added to the culture nedis at concontrstionsof 26 u91ml (105 and 88 uM rrrpectively),approximately50% of the culturedembryos were malformed. The pred~ln~nt ~lfor~ttons observedwere ventrolsterdlprotrusionsand hypoplasiaof thQ prosencephslon. When reduced g~ut~thione(up to 4.0 II@)was added to the embryo cultun, medium containingAAAF (88uM),the percentageof malformedembryos decreasedin a concentration-dependent swnner. HowQver,minimal changes in Qmbr~onalgrowth]pdriIIketeVS w@rQ observed. Concentrationsof glut~thioneabova 4.0 mN wQre toxic to thr culturedembryos.
We have also examined thQ affects of adding a sulfationsystem (3'0phosphoadenosineG'=phosphosulf~te, 0.25 mN, plus rat hepatlc 104.~0 x g-hr supernat~n~)to culture media system was present,a higher containingday 10 rat embryos and N-OH-AAF. When a cornplate rate of mslformedembryos was observed thsn when an Incompletesystsm was present. However, & slmf1Qr type of cephalic~lfor~tion was seen under both condutions, The results SUggQStQd thst resctlveelQctrophiteowere responsiblefor the metaboltteQllCltad IBQIformmtlons. Supportedby NIH Grants MD-04839,EH=D7032,MD-12717 and HO-tlOG36,
MARONI, M.,
COLOMBI, A.,
FERIOLI, A.,
A DOSE-RESPONSE STUDY
AND FOA’, V.
XNSTITUTg FOR OCCUPATIONALHEALTH - UNIVERSITY OF MILAN (ITALY). 20122 MILANO, Urinery
VIA S.
BARNABA8
excretion
of D-glucaric acid @LA) and porphyrins from 8 to 4 carboxylic were measured in 51 PCB workers to determlne whether they were associated with the blood total PC6 concentrations in the workers and whether any aeeociation could be established among theee parameters. Mran GGT activity (27.8 U/L) and urinary GLA (71.7smolA.)and total porphyrin (93A sg/L) excretion were all increased when compared to reference values. Rlcod total PCB concentration, determined by packed column CLC, ranged from 88 to 1359 ppb I’nr the 28 workere for whom this meaeurement wae available. To achieve a normal dfstributlon, all the variables were transformed into log, velucs. No sinniftcant association was found either between GLA end GCT or single and total porphyrin homologues and the blood PCB concentration, A poeitive eaeociation (r=0,46g, PzO.01) was observed between individual valuea of GGT and GLA, Urinary GLA excretion poeitively correlated with f-COOH porphyrin excretion (r-0.416, P
gruupe and aerum GGT activity
#j ANALYSIS OF THE EFFECTS OF CONJUGATIONON THE T~RATOG~N~C~TY OF ANDNATiCAMfNES
IN
VITRO. FAUSTMAN-WATTS,E,T, GREENAWAY,J.C.2, WALKER, 5.2, FANTEL, A.G.2, JUCHAU, H.R.l.
DEPARTMENTSOF PHARMACOLOGY1AND PEDIATRICS2SCHOOL OF MEDICIINE, LMIVEHSITYDF WASHINGTON,SEATTLE,WA 98195
The objectiveof this study w&s to initiatean ex~tnin~t~on of the effect of conjugation on the terstogenicity-in vitro of 2=scetylsminofluorene metabolites. Sprtiuuu-Hawley rat embryoswere explantedon day 10 and cultured for 24 hours. Dur previouswork has shown thst when either N-~dro~=2~~etyl8m~nofluor~ne (N-OW-AAF)or N=aceto~=2=d~@tyl= aminofluorene(AAF) were added to the culture nedis at concontrstionsof 26 u91ml (105 and 88 uM rrrpectively),approximately50% of the culturedembryos were malformed. The pred~ln~nt ~lfor~ttons observedwere ventrolsterdlprotrusionsand hypoplasiaof thQ prosencephslon. When reduced g~ut~thione(up to 4.0 II@)was added to the embryo cultun, medium containingAAAF (88uM),the percentageof malformedembryos decreasedin a concentration-dependent swnner. HowQver,minimal changes in Qmbr~onalgrowth]pdriIIketeVS w@rQ observed. Concentrationsof glut~thioneabova 4.0 mN wQre toxic to thr culturedembryos.
We have also examined thQ affects of adding a sulfationsystem (3'0phosphoadenosineG'=phosphosulf~te, 0.25 mN, plus rat hepatlc 104.~0 x g-hr supernat~n~)to culture media system was present,a higher containingday 10 rat embryos and N-OH-AAF. When a cornplate rate of mslformedembryos was observed thsn when an Incompletesystsm was present. However, & slmf1Qr type of cephalic~lfor~tion was seen under both condutions, The results SUggQStQd thst resctlveelQctrophiteowere responsiblefor the metaboltteQllCltad IBQIformmtlons. Supportedby NIH Grants MD-04839,EH=D7032,MD-12717 and HO-tlOG36,