Possible mechanisms underlying mammary carcinogenesis in female Wistar rats by nitrofurazone.
Mechanisms underlying mammary carcinogenesis in female rat given nitrofurazone (NF) were examined. Experiment I: female Wistar rats were divided into three groups, and given diets containing 0, 500 or 1000 ppm NF for 5 weeks. At terminal sacrifice, body and uterus weights were the same in all groups, although ovary weights in NF-treated animals were significantly higher than in control animals, the increase being dose-dependent. Serum prolactin (PRL) concentrations in NF-treated groups at 17:00 h on the day of proestrus were also dose-dependently higher than that in control group. Experiment II: a two-stage rat mammary carcinogenesis protocol was performed. Rats were divided into four groups, Groups 2 and 4 being treated by 9,10-dimethyl-1,2-benzanthracene (DMBA) at 7-weeks-old. Groups 3 and 4 were given diets containing 1000 ppm of NF between 8 and 27 weeks of age, when all surviving rats were autopsied. DMBA-treated animals demonstrated mammary tumors at high incidences, 91.1 and 90.5%, respectively, in Groups 2 and 4, no tumor development being observed without the initial carcinogen exposure (Groups 1 and 3). The mean tumor weights and the mean numbers of tumors per tumor-bearing rats in Group 4 were increased as compared with Group 2, albeit not significantly. Serum PRL (proestrus day at 17:00 h) and progesterone (PG) (diestrus day at 10:00 h) concentrations in NF-treated animals (Groups 3 and 4) were significantly higher than those in untreated rats (Groups 1 and 2). These results suggest that increases of serum PRL and PG concentrations by NF may be the most important factors regarding its promotion of mammary tumor growth and/or enhancement of mammary carcinogenesis in female rats.
Takahashi
M
M
Department of Pathology, Sasaki Institute, 2-2 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
Iizuka
S
S
Watanabe
T
T
Yoshida
M
M
Ando
J
J
Wakabayashi
K
K
Maekawa
A
A
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004031:Diestrus / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced*; D009583:Nitrofurazone / Q000633:toxicity*; D011359:Proestrus / Q000097:blood / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood
D000891:Anti-Infective Agents, Local; D002273:Carcinogens; D011374:Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D009583:Nitrofurazone