The mechanisms by which cadmium and certain other metals induce cancer are currently under study at various levels. On the level of the whole animal, association of oral cadmium exposure and neoplasia of the rat prostate was confirmed, an important advance in support of cadmium as a factor in human prostatic cancer. Dietary zinc deficiency was found to either enhance or suppress cadmium carcinogenesis depending on the route of exposure to cadmium and/or the specific target tissue. The F344 rat was found to be particularly susceptible to sarcoma at the site of cadmium injection, indicating a genetic basis of susceptibility to tumor formation even at this target site. On the cellular and molecular level, it was found that cadmium is clearly capable of producing profound DNA damage, including frequent DNA single strand breakage. Pretreatments, such as zinc, which prevent cadmium carcinogenesis in certain tissues also prevent these genotoxic effects of cadmium. In testicular interstitial cells, several studies were directed at identifying factors involved in chemically-induced or genetically-based resistance. Testicular interstitial cells from strains of mice resistant to the effects of cadmium on the testes showed less cadmium uptake and more efflux than cells from susceptible mice. On the molecular level, it was determined that the testicular metallothionein gene does not play a major role in tolerance to cadmium carcinogenesis induced by pretreatment with zinc, as no differences in metallothionein mRNA levels were detected in tolerant cells. These findings support the concept that unresponsiveness to induction of the metallothionein gene is a consistent finding in target tissues of cadmium carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005488-06
Application #
3853469
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code