Tumorigenicity of five dihydrodiols of benz(a)anthracene on mouse skin: exceptional activity of benz(a)anthracene 3,4-dihydrodiol.
Benz[a]anthracene and the five metabolically possible vicinal trans dihydrodiols of benz[a]anthracene were tested for ability to initiate skin tumors in CD-1 female mice. A single topical application of 0.4-2.0 mumol of hydrocarbon was followed 18 days later by twice weekly applications of the skin promoter 12-O-tetradecanoylphorbol-13-acetate. Comparisons of latency period, percent of mice with tumors, and number of papillomas observed per mouse indicated that benz[a]anthracene 1,2-, 5,6-, 8,9-, and 10, 11-dihydrodiols were all less active tumor initiators than was benz[a]anthracene. The high tumorigenicity of benz[a]anthracene 3,4-dihydrodiol, presumably the result of metabolism to either or both of the diastereomeric benz[a]anthracene 3,4-diol-1,2-epoxides, supports the bay region theory of polycyclic hydrocarbon carcinogenicity and provides the first example of a proximate carcinogenic metabolite that is much more active than the parent hydrocarbon on mouse skin.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D005260:Female; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012867:Skin / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes
Cancer Res. 1976 Sep;36(9 pt.1):3358-66
788899
Proc Natl Acad Sci U S A. 1977 Jul;74(7):2746-50
331315
Nature. 1977 Mar 24;266(5600):378-80
859608
Biochem Biophys Res Commun. 1976 SEP 20;72(2):680-6
791280
Proc Natl Acad Sci U S A. 1976 Nov;73(11):3867-71
1069271
FEBS Lett. 1974 Oct 1;47(1):30-3
4154213
Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135-9
1061098
Proc Natl Acad Sci U S A. 1976 Mar;73(3):950-4
768988
Adv Cancer Res. 1974;20:165-274
4617500
Chem Biol Interact. 1973 Mar;6(3):189-202
4632460
Nature. 1974 Nov 22;252(5481):326-8
4473724
Adv Cancer Res. 1975;21:391-425
174398
FEBS Lett. 1974 Oct 1;47(1):34-8
4426394
Science. 1974 Aug 16;185(4151):573-82
4841570
J Natl Cancer Inst. 1973 Feb;50(2):369-80
4702111
Cancer Res. 1970 Mar;30(3):559-76
4915745
Biochem Biophys Res Commun. 1975 Sep 16;66(2):693-700
1101891
Proc Natl Acad Sci U S A. 1976 Feb;73(2):607-11
1061161
Proc Natl Acad Sci U S A. 1976 Jan;73(1):243-7
1061121
Nature. 1976 May 6;261(5555):52-4
1272374
Cancer Res. 1975 May;35(5):1375-7
1120318
Biochem J. 1964 Sep;92(3):631-8
5891198
Biochem J. 1964 Jun;91(3):493-506
5840709