Time-dependent Inhibition by 2,3,7,8-Tetrachlorodibenzo-p-dioxin of Skin Tumorigenesis with Polycyclic Hydrocarbons

摘要: Abstract The effects of treating female mice with single topical doses 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) at various times before and after 7,12-dimethylbenz( a )anthracene (DMBA), benzo( )pyrene, 3-methylcholanthrene (MCA), (±)- trans -7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo( )-pyrene were studied. TCDD, 1 µg/mouse, was applied topically 3 days prior to, 5 min or day the initiator. application TCDD to initiation DMBA, MCA had little no effect on papilloma formation. In contrast, when these hydrocarbons, marked reduction in formation observed. )pyrene produced 81, 50, 39% inhibition 20 weeks promotion. Similar observed higher initiating DMBA diol-epoxide utilized. addition, i.p. (1 µg/mouse) highly effective inhibiting Several congeners lacking, possessing similar, different inducing properties, tested for their tumor by DMBA. 3,4,3′,4′-Tetrachlorobiphenyl effectively inhibited whereas 2,7-dichlorodibenzo- 2,4,5,2′,4′,5′-hexachlorobiphenyl response. Topical utilized experiments markedly induced epidermal aryl hydrocarbon hydroxylase (21-fold) treatment. uridine diphosphoglucuronyltransferase activities stimulated 2- 3-fold following treatment epoxide hydrase glutathione- S -transferase activities. time course induction correlated inhibitory MCA.