Marked Differences in the Skin Tumor-initiating Activities of the Optical Enantiomers of the Diastereomeric Benzo(a)pyrene 7,8-Diol-9,10-Epoxides

T. J. Siaga, W. J. Bracken, G. Gleason, W. Levin, A. H. Conney, H. Yagi, D. M. Jerina

Research output: Contribution to journalArticlepeer-review

Abstract

The abilities of the optically pure (+)-and (-)-enantiomers of the diastereomeric 7,8-dihydroxy-9,10-epoxy-7.8.9.10-tetrahydrobenzo(a)pyrenes derived from the enantiomeric frans-7,8-dihydrodiols to initiate skin tumors in mice were determined with a two-stage system of tumorigenesis. As a tumor initiator, (+)-7ß,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene 2 was approximately 60% as active as was benzo(a)pyrene, whereas (-)-7α,8ß-dihydroxy-9ß,10ß-epoxy-7,8,9,10-tetrahydrobenzo- (a)pyrene 2 was about 2% as active as was benzo(a)pyrene. The racemic mixture of the above diol-epoxide, in which the 9,10-epoxide is trans to the 7-hydroxyl group, was 25% as active as was benzo(a)pyrene as a tumor initiator. (-)-7ß,8α-Dihydroxy-9ß,10ß-epoxy-7,8,9,10-tetrahydrobenzo- (a)pyrene 1 and (+)-7α,8ß-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene 1, in which the 9,10-epoxide is cis to the 7-hydroxyl group, were found to have little or no tumorigenic activity. The tumor-initiating ability of (+)-7ß,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene 2 was found to be greater when given daily for 6 days at a dose of 34 nmol/day than when given once at a 200-nmol dose level. Similar fractionated doses of benzo(a)pyrene or (-)-7α,8ß-dihydroxy-9ß,10ß-epoxy-7.8.9.10-tetrahydrobenzo(a)pyrene 2 did not increase their skin tumor-initiating activity. The data suggest that (+)-7ß,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo- (a)pyrene is an ultimate carcinogenic form of benzol-pyrene.

Original languageEnglish (US)
Pages (from-to)67-71
Number of pages5
JournalCancer Research
Volume39
Issue number1
StatePublished - Jan 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Marked Differences in the Skin Tumor-initiating Activities of the Optical Enantiomers of the Diastereomeric Benzo(a)pyrene 7,8-Diol-9,10-Epoxides'. Together they form a unique fingerprint.

Cite this