Metabolic activation of 3-methylcholanthrene in mouse skin: fluorescence spectral evidence indicates the involvement of diol-epoxides formed in the 7,8,9,10-ring.
Hydrolysates of DNA that had been isolated from mouse skin treated with 3H-labelled 3-methylcholanthrene were subjected to chromatography on Sephadex LH20 columns and 3H-labelled products that eluted in the region expected for nucleoside-hydrocarbon adducts were purified further by high pressure liquid chromatography; eight major and one minor products were resolved and their fluorescence spectra were determined using photon-counting spectrophotofluorimetry. The fluorescence spectra of six of the major products are anthracene-like and are similar to the previously-reported spectrum of 7,8,9,10-tetrahydro-3-methylcholanthrene, a result that is consistent with metabolic activation involving diol-epoxide formation in the 7,8,9,10-ring of 3-methylcholanthrene. The fluorescence spectra of the other two major products are also anthracene-like, but their maxima are shifted to longer wavelengths relative to the maxima in the spectrum of 7,8,9,10-tetrahydro-3-methylcholanthrene. The minor product possesses a fluorescence spectrum that is not anthracene-like and that is dissimilar from the spectra of products formed from 3-methylcholanthrene 11,12-oxide.
Cooper
C S
CS
Institute of Cancer Research, Royal Cancer Hospital, London, UK.
Vigny
P
P
Kindts
M
M
Grover
P L
PL
Sims
P
P
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D012867:Skin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D018736:DNA Adducts; D008748:Methylcholanthrene; C038099:9,10-dihydroxy-7,8-epoxy-7,8,9,10-tetrahydro-3-methylcholanthrene; D004247:DNA