High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice.
We studied the effect of dietary retinoic acid (RA) in a two-stage protocol of skin carcinogenesis in female SENCAR mice. At 3 weeks of age mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and promoted with either 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms) once per week or mezerein (MEZ, 4 micrograms) twice per week for 20 weeks. At the week of DMBA initiation mice were also put on a purified diet containing either 3 (physiological dose) or 30 micrograms (pharmacological dose) of RA/g of diet. High dietary RA significantly inhibited papilloma yield but not incidence in the MEZ-promoted group. Papilloma incidence and yield were also lower in the MEZ- than in the TPA-treated groups. Cumulative carcinoma incidence and yield, and conversion efficiency (= (carcinomas/maximal papillomas) x 100%), were all decreased by high dietary RA in both MEZ- and TPA-treated groups. These results demonstrate that high dietary RA inhibited skin carcinogenesis in MEZ-promoted mice at the stages of tumor promotion and malignant conversion, while this inhibition occurred only at the malignant conversion stage in TPA-promoted mice.
Chen
L C
LC
Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892, USA.
Tarone
R
R
Huynh
M
M
De Luca
L M
LM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced* / Q000517:prevention & control; D004032:Diet; D004224:Diterpenes; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D010212:Papilloma / Q000139:chemically induced* / Q000517:prevention & control; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D013729:Terpenes; D014212:Tretinoin / Q000008:administration & dosage*
D002273:Carcinogens; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene