Persistence of prostatic intraepithelial neoplasia after effective chemoprevention of microscopic prostate cancer with antiandrogen in a rat model.
OBJECTIVE
We determined the chemopreventive effect of the antiandrogen bicalutamide (Zeneca Co., Ltd., Osaka, Japan) on Fisher 344 rat prostate carcinogenesis induced by DMAB (3,2'-dimethyl-4-aminobiphenyl) (Nard Co., Ltd., Osaka, Japan). We have previously reported that rat prostate microscopic carcinogenesis in this model was paradoxically enhanced when continuous treatment with bicalutamide was begun 20 weeks after the initiation of DMAB. In the current study we determined whether antiandrogen would promote or suppress the prostate carcinogenesis when administration was begun at a later period of carcinogenesis.


METHODS
DMAB at a dose of 50 mg/kg was injected subcutaneously into all animals 10 times at 2-week intervals. To clarify the target lesions of bicalutamide we used 2 control groups (groups 1 and 2). Animals in groups 1 and 2 were autopsied at 60 and 74 weeks, respectively, after the initiation of DMAB. Treatment with bicalutamide began in the 60th week in group 3 rats and continued for 14 weeks. They were sacrificed in the 74th week.


RESULTS
Microscopic cancer was revealed in 27% of group 1 rats and the incidence was increased to 42% in group 2 (statistically not significant). Delayed bicalutamide treatment significantly suppressed the cancer lesion. No cancerous lesion was detected in the ventral or other lobes of the prostate of the rats in group 3. In contrast, bicalutamide did not affect the incidence of PIN. The difference in the incidence of PIN in groups 2 and 3 (84% and 78%, respectively) was not significant.


CONCLUSIONS
The current investigation indicates that, if bicalutamide is started in the later period, it can efficiently eradicate existing microscopic cancer. Despite this suppressive effect on microscopic cancer bicalutamide permits the persistence of PIN. The latter finding suggests that the sensitivity of PIN to antiandrogen might be more complicated than previously recognized.
Yamauchi
Atsushi
A
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan. a-yamauchi@chubyoin.pref.ibaraki.jp
Kawai
Koji
K
Tsukamoto
Sadamu
S
Ideyama
Yukitaka
Y
Shirai
Tomoyuki
T
Akaza
Hideyuki
H
D000611:Aminobiphenyl Compounds / Q000008:administration & dosage; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage; D004195:Disease Models, Animal; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009570:Nitriles; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy* / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D014105:Tosyl Compounds
D000611:Aminobiphenyl Compounds; D000726:Androgen Antagonists; D000813:Anilides; D002273:Carcinogens; D009570:Nitriles; D014105:Tosyl Compounds; C001042:2',3-dimethyl-4-aminobiphenyl; C053541:bicalutamide