TY - JOUR
T1 - Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters
AU - Wei, Huachen
AU - Frenkel, Krystyna
N1 - Funding Information:
This research was supported by National Cancer Institute, USPHS Grants No, CA 37858 and CA 49798 (its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National fin m Institute); by NIEHS Cancer Center Grant No. ES 00260; and by a training grant from the Sackler Institute of Biochemical Sciences, New York University Medical Center. Presented in part at the 1992 Annual Meeting of the American Association for Cancer Research (Proc. Am. Assoc. Cancer Res., 33, 179, 1992).
PY - 1993/6
Y1 - 1993/6
N2 - Reactive oxygen species (ROS) have been implicated as being involved in tumor promotion processes. However, the mechanism by which ROS modulate tumor promotion has not as yet been elucidated. In this report, we show that phorbol ester-type tumor promoters (12-O-tetradecanoyl-phorbol-13-acetate [TPA], mezerein and 12-O-retinoylphor-bol-13-acetate [RPA]), which vary in their in vivo potencies, also differ in their effect on formation of hydrogen peroxide (H2O2) and oxidation of normal bases to 5-hydroxymethyl-2'-deoxyuridine [HMdU] and 8-hydroxyl-2'-deoxyguanosine [8-OHdG] in the DNA of SENCAR mouse epidermis, though they are equipotent in causing infiltration of polymorpho-nuclear leukocytes (PMNs). Treatment of SENCAR mice with the chemopreventive agents (-)-epigallocatechin gallate or tamoxifen (6.5 nmol) prior to application of TPA (6.5 nmol) diminished PMN infiltration, and formation of H2O2, HMdU and 8-OHdG. These results strengthen the evidence that ROS are involved in tumor promotion, and that generation of ROS and the subsequent oxidative DNA modification are related to the tumor-promoting potencies of the different phorbol ester-type promoters.
AB - Reactive oxygen species (ROS) have been implicated as being involved in tumor promotion processes. However, the mechanism by which ROS modulate tumor promotion has not as yet been elucidated. In this report, we show that phorbol ester-type tumor promoters (12-O-tetradecanoyl-phorbol-13-acetate [TPA], mezerein and 12-O-retinoylphor-bol-13-acetate [RPA]), which vary in their in vivo potencies, also differ in their effect on formation of hydrogen peroxide (H2O2) and oxidation of normal bases to 5-hydroxymethyl-2'-deoxyuridine [HMdU] and 8-hydroxyl-2'-deoxyguanosine [8-OHdG] in the DNA of SENCAR mouse epidermis, though they are equipotent in causing infiltration of polymorpho-nuclear leukocytes (PMNs). Treatment of SENCAR mice with the chemopreventive agents (-)-epigallocatechin gallate or tamoxifen (6.5 nmol) prior to application of TPA (6.5 nmol) diminished PMN infiltration, and formation of H2O2, HMdU and 8-OHdG. These results strengthen the evidence that ROS are involved in tumor promotion, and that generation of ROS and the subsequent oxidative DNA modification are related to the tumor-promoting potencies of the different phorbol ester-type promoters.
UR - http://www.scopus.com/inward/record.url?scp=0027153961&partnerID=8YFLogxK
U2 - 10.1093/carcin/14.6.1195
DO - 10.1093/carcin/14.6.1195
M3 - Article
C2 - 8508507
AN - SCOPUS:0027153961
SN - 0143-3334
VL - 14
SP - 1195
EP - 1201
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -