N-(4-hydroxyphenyl)all-trans-retinamide (4-HPR) high dose effect on DMBA-induced hamster oral cancer: a histomorphometric evaluation.
N-(4-hydroxyphenyl)all-trans-retinamide (4-HPR) has shown cancer chemoprevention activity in many experimental and clinical situations. The purpose of this research is to evaluate the in vivo efficacy of 4-HPR in preventing 7,12-dimethylbenz(alpha)antracene (DMBA)-induced oral carcinogenesis and to study histomorphometric changes. 76 Syrian hamsters were separated into four groups: group 1, untreated controls (16 animals); group 2, 4-HPR controls (16 animals); group 3, DMBA-treated animals (28); group 4, animals treated with DMBA and 4-HPR (16). Hamsters were painted with a 0.5% solution of DMBA three times a week in their left buccal pouch. A diet of 2 mmol of 4-HPR/kg was administered. At week 9, 50% of the animals were killed; the remainder were killed at week 12. Pathology and histomorphometric tests were performed on epithelium, dysplasia and carcinomas. At week 9, 5 carcinomas were found in group 3, and 13 in group 4. Cancers in group 4 were more numerous, endophytic and infiltrating than those in group 3 animals. At week 12, 16 carcinomas were detected in group 3 animals, but group 4 developed more carcinomas per animal than group 3. Using these experimental concentrations, 4-HPR cannot express its best chemopreventive effect.
Lajolo
C
C
School of Dentistry, Catholic University, Largo A. Gemelli, 8; I-00168, Rome, Italy. carlo.lajolo@fastwebnet.it
Giuliani
M
M
Sgambato
A
A
Majorano
E
E
Lucchese
A
A
Capodiferro
S
S
Favia
G
G
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects*; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001284:Atrophy; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D018890:Chemoprevention; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D006224:Cricetinae; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D017313:Fenretinide / Q000008:administration & dosage / Q000627:therapeutic use*; D006965:Hyperplasia; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D009361:Neoplasm Invasiveness; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017313:Fenretinide; D015127:9,10-Dimethyl-1,2-benzanthracene