TY - JOUR
T1 - Mutagenicity, metabolism and DNA adduct formation of 6-nitrochrysene in Salmonella lyphimurium
AU - El-bayoumy, Karam
AU - Delcios, K. Barry
AU - Heflich, Robert H.
AU - Walker, Ralph
AU - Shiue, Gong Huey
AU - Hecht, Stephen S.
N1 - Funding Information:
This study was supported by National Cancer Institute Grant CA 35519. This is paper 123 of the series 'A Study of Chemical Carcinogenesis'.
PY - 1989/5
Y1 - 1989/5
N2 - The mutagenic activities of 6-nitrochrysene (6-NC) and its previously identified metabolites were evaluated in Salmonella typhimurium TA100 and TA98 in the presence and absence of metabolic activation by 9000 g supernatant from the livers of rats treated with Aroclor. 6-Aminochrysene (6-AC) and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (1,2-DHD-6-AC) were the most active mutagens in TA100 upon metabolic activation. 6-NC and 6-AC were the most active mutagens in TA100 in the absence of metabolic activation. Upon metabolic activation, 6-AC was the most active in TA98; the other compounds were weak or inactive depending on the conditions of the assay. in the absence of metabolic activation, the mutagenic activities of 6-NC and its metabolites in TA98 were comparable to those observed in TA100. The major metabolite formed upon incubation of [3H]6-NC with S.typhimurium TA100 and 9000 g supernatant from the livers of Aroclor-induced rats was identified as trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene (1,2-DHD-6-NC); trans-9, 10-dihydro-9, 10-dihydroxy-6-nitrochrysene and 1,2-dihydroxy-6-nitrochrysene were also identified. The major DNA adduct formed in TA100 under these conditions was chromatographically identical to that previously detected in vivo in the liver and lungs of newborn mice treated with 6-NC, as well as to that obtained upon incubation of 1,2-DHD-6-AC with calf thymus DNA in the presence of rat liver microsomes. The DNA adducts derived from 6-NC in S.typhimurium TA100 without activation were identical to those adducts previously identified after incubation of 6-hydroxylaminochrysene with calf thymus DNA. The results of this study support our hypothesis that the mammalian metabolic activation of 6-NC occurs via ring oxidation to 1,2-DHD-6-NC, nitroreduction to 1,2-DHD-6-AC and, finally, epoxidation to a bay region diol epoxide.
AB - The mutagenic activities of 6-nitrochrysene (6-NC) and its previously identified metabolites were evaluated in Salmonella typhimurium TA100 and TA98 in the presence and absence of metabolic activation by 9000 g supernatant from the livers of rats treated with Aroclor. 6-Aminochrysene (6-AC) and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (1,2-DHD-6-AC) were the most active mutagens in TA100 upon metabolic activation. 6-NC and 6-AC were the most active mutagens in TA100 in the absence of metabolic activation. Upon metabolic activation, 6-AC was the most active in TA98; the other compounds were weak or inactive depending on the conditions of the assay. in the absence of metabolic activation, the mutagenic activities of 6-NC and its metabolites in TA98 were comparable to those observed in TA100. The major metabolite formed upon incubation of [3H]6-NC with S.typhimurium TA100 and 9000 g supernatant from the livers of Aroclor-induced rats was identified as trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene (1,2-DHD-6-NC); trans-9, 10-dihydro-9, 10-dihydroxy-6-nitrochrysene and 1,2-dihydroxy-6-nitrochrysene were also identified. The major DNA adduct formed in TA100 under these conditions was chromatographically identical to that previously detected in vivo in the liver and lungs of newborn mice treated with 6-NC, as well as to that obtained upon incubation of 1,2-DHD-6-AC with calf thymus DNA in the presence of rat liver microsomes. The DNA adducts derived from 6-NC in S.typhimurium TA100 without activation were identical to those adducts previously identified after incubation of 6-hydroxylaminochrysene with calf thymus DNA. The results of this study support our hypothesis that the mammalian metabolic activation of 6-NC occurs via ring oxidation to 1,2-DHD-6-NC, nitroreduction to 1,2-DHD-6-AC and, finally, epoxidation to a bay region diol epoxide.
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U2 - 10.1093/mutage/4.3.235
DO - 10.1093/mutage/4.3.235
M3 - Article
C2 - 2659942
AN - SCOPUS:0024518121
SN - 0267-8357
VL - 4
SP - 235
EP - 240
JO - Mutagenesis
JF - Mutagenesis
IS - 3
ER -