Abstract:
:The rat liver 9000 g supernatant mediated metabolism of the carcinogenic aristolochic acid, which consists of aristolochic acid I (AAI) and aristolochic acid II (AAII), was investigated. Under anaerobic conditions the major metabolites were the corresponding aristolactams for both AAI and AAII. In contrast under aerobic conditions AAII was not detectably metabolized and the only metabolite found for AAI was the O-demethylated derivative aristolochic acid Ia (AAIa). The metabolites were identified by their u.v., mass and n.m.r. spectra and by comparison with reference standards. The mutagenic activities of the three metabolites were determined in Salmonella typhimurium strains TA1537 and TA 100. The aristolactams were mutagenic in both strains when a metabolizing system was present. These results indicate that AAI or AAII and their aristolactams exert their effect via a common reactive intermediate, probably the corresponding hydroxylamine. AAIa was only very weakly mutagenic and this metabolite may therefore not be regarded as a major mutagenic metabolite of AAI. These findings suggest that the acids are preferentially metabolized by two totally different pathways in vitro, namely an oxidative pathway for AAI and a reductive pathway for AAII.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Schmeiser HH,Pool BL,Wiessler Mdoi
10.1093/carcin/7.1.59subject
Has Abstractpub_date
1986-01-01 00:00:00pages
59-63issue
1eissn
0143-3334issn
1460-2180journal_volume
7pub_type
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