Apparent quiescence of the metallothionein gene in the rat ventral prostate: association with cadmium-induced prostate tumors in rats.
Several chronic studies in rats indicating that cadmium exposure can induce tumors of the ventral prostate have recently been completed in our laboratory. In one such study, a single dose of cadmium, s.c., increased prostatic tumor incidence only at doses below 5.0 mumol/kg, the approximate threshold for cadmium-induced testicular damage. In a further study, prostatic tumors were elevated with higher doses of cadmium (30 mumol/kg, s.c.) if testicular damage was prevented by zinc pretreatment. Most recently, we found that dietary cadmium (25 to 200 micrograms/g) also can increase prostatic neoplastic lesions, but these were reduced by zinc-deficient diets. Thus it appears that cadmium produces prostatic tumors only if testicular function is maintained. Furthermore, we find that metallothionein (MT), a protein associated with cadmium tolerance, may be deficient in the rat prostate, and the prostatic MT gene, at least in the ventral lobe, is unresponsive to metal stimuli. In liver, MT gene expression, as assessed by MT-1 mRNA, was quite apparent in control tissue and was induced in a dose-dependent manner 24 hr following cadmium exposure (1 to 10 mumol/kg, s.c.). However, in the ventral prostate very low constitutive levels of MT-1 mRNA were detected and increases did not occur with cadmium exposure. Cadmium concentrations in the ventral prostate were in excess of those that cause significant induction in the liver. In sharp contrast to the gene in the ventral prostate, in the dorsal prostate the MT gene was quite active. The dorsal prostate is not susceptible to cadmium carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland.
T P
TP
Coogan
N
N
Shiraishi
M P
MP
Waalkes
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D002104:Cadmium; D008668:Metallothionein