TPA decreases the p53 response to benzo[a]pyrene-DNA adducts in vivo in mouse skin.
TPA, a well-known tumor promoter, decreased the response of nuclear p53 immunoreactivity to benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts in C57BL/6 mouse skin in vivo. A dose-dependent increase in both the level of BPDE-DNA adducts and nuclear p53 immunoreactivity was found in mice treated topically with 50-750 microg benzo[a]pyrene. Such a positive correlation between the adducts and p53 positivity was suggested by an earlier study. Since p53 probably functions in DNA damage control, interference by TPA with the p53 response could be a mechanism in TPA-induced tumor promotion. Whether such a mechanism is more general in tumor promotion deserves further study.
Tapiainen
T
T
Department of Pharmacology, University of Oulu, Finland.
Järvinen
K
K
Pääkko
P
P
Bjelogrlic
N
N
Vähäkangas
K
K
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000276:immunology
D002273:Carcinogens; D018736:DNA Adducts; D016159:Tumor Suppressor Protein p53; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D013755:Tetradecanoylphorbol Acetate