Iron lactate induction of pancreatic and endometrial proliferative lesions and a lack of increased tumors in a 104-week carcinogenicity study in F344 rats.
Iron lactate has been used as a food additive for iron supplementation. The present study was conducted to determine whether it might have carcinogenic potential. A total of 150 male and 150 female Fischer 344 rats were divided into three groups and fed basal diet containing 0, 1 or 2% of iron lactate for 104 weeks. No iron lactate-induced tumors were observed in any groups, although the incidences of pancreatic acinar cell and endometrial gland hyperplasias were increased in males and females, respectively, in the 2% group. Thus our in vivo animal data indicate that iron lactate lacks carcinogenicity in male and female F344 rats. However, estrogenic effects might be concluded based on the data for endometrial lesions. In a second experiment, an estrogen responsive rat pituitary tumor cell line, MtT/Se, and a human breast cancer cell line, MCF-7, were therefore employed to examine the estrogenic potential of iron lactate with regard to receptor binding affinity and ERE-reporter gene activation. Results in both cases were negative. Further investigations are needed to elucidate the mechanisms of induction of pancreatic and endometrial proliferative lesions by iron lactate.
Imai
T
T
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. imai@nihs.go.jp
Yasuhara
K
K
Matsui
H
H
Maruyama
S
S
Fujimoto
N
N
Mitsumori
K
K
Hirose
M
M
D000818:Animals; D015197:Carcinogenicity Tests; D016889:Endometrial Neoplasms / Q000139:chemically induced*; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005503:Food Additives / Q000633:toxicity; D006801:Humans; D058085:Iron Compounds / Q000378:metabolism / Q000633:toxicity*; D007773:Lactates / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements; D012727:Sex Characteristics; D013997:Time Factors; D014316:Tritium; D014407:Tumor Cells, Cultured
D004967:Estrogens; D005503:Food Additives; D058085:Iron Compounds; D007773:Lactates; D011960:Receptors, Estrogen; D014316:Tritium; D004958:Estradiol