Cadmium exposure in rats and tumours of the prostate.
Recently, we completed three chronic studies in rats indicating that cadmium exposure can induce tumours of the prostate. In the first study, s.c. cadmium exposure increased prostatic tumour incidence only at doses below the threshold for cadmium induction of testicular dysfunction (5.0 mumol/kg). In a second study, prostatic tumours were elevated at higher doses of cadmium (30 mumol/kg, s.c.) if testicular dysfunction was prevented by zinc treatment. Finally, dietary cadmium (25-200 micrograms/g) increased prostatic neoplastic lesions. Thus it appears that cadmium produces prostatic tumours only if testicular function is maintained. Accumulation and retention of prostatic cadmium appears to be highly androgen-dependent. Furthermore, metallothionein, a protein associated with tolerance to cadmium, may be deficient in the rat prostate, and the prostatic metallothionein gene, at least in the ventral lobe, may be unresponsive to metal stimuli. The finding of prostatic cancer in cadmium-treated rats clearly supports a possible role for exposure to cadmium in human prostatic cancer.
Waalkes
M P
MP
Inorganic Carcinogenesis Section, Frederick Cancer Research and Development Center, MD 21702.
Rehm
S
S
Perantoni
A O
AO
Coogan
T P
TP
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008668:Metallothionein / Q000235:genetics; D008670:Metals / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology; D015032:Zinc / Q000172:deficiency
D008670:Metals; D002104:Cadmium; D013739:Testosterone; D008668:Metallothionein; D015032:Zinc