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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1985-1-24
pubmed:abstractText
The metabolic fate of the bacterial mutagen, environmental pollutant and potential carcinogen 1-nitropyrene (NP) has been investigated in the rat. Over half of an i.p. dose (10 mg/kg) of 1-nitro[14C]pyrene was excreted within 24 h of dosing, 15% of the dose in urine and 40% in the faeces. After 96 h greater than 80% of the dose had been recovered. The urinary and fecal metabolites of NP were separated and quantitated by h.p.l.c., then identified by high resolution gas chromatography/mass spectrometry (h.r.g.c./m.s.) and comparison with synthetic reference compounds, where available. Very little (less than 5%) of the dose was excreted unchanged. Urinary metabolites were all excreted in conjugate form, mainly with glucuronic acid. Among the principal metabolite fractions identified were 3-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene (already known as hepatic in vitro metabolites of 1-nitropyrene) and the hitherto unreported metabolites 6-hydroxy-N-acetyl-1-aminopyrene and 8-hydroxy-N-acetyl-1-aminopyrene. Mutagenic activity was detected, by means of the Ames Salmonella (strain TA 98) plate incorporation assay, in the urine of rats dosed with NP. This mutagenicity, unlike that of NP itself, required exogenous metabolic activation. It was predominantly associated with 6-hydroxy-N-acetyl-1-aminopyrene and with the nitropyrene phenols (specific mutagenicity 600 and 700 rev/nmol respectively in the presence of 0.6 mg of S9 protein per plate). The majority of the residual metabolites were polar, refractory to enzymic hydrolysis, and of low mutagenicity. The major proportion of the 14C in feces was not extractable or amenable to enzymic hydrolysis; the extractable fecal metabolites were similar in nature to those in urine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1557-64
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Metabolism of 1-nitro[14C]pyrene in vivo in the rat and mutagenicity of urinary metabolites.
pubmed:publicationType
Journal Article