Cadmium and dimethylnitrosamine as synergists in carcinogenesis
A two part study was conducted with male Wistar rats to investigate possible synergism in carcinogenesis between Cd and dimethylnitrosamine (DMN). In Series I, rats received an intraperitoneal dose of DMN followed at 4 hours and at 4 days by intramuscular injections of CdCl/sub 2/. Series II rats received a series of intramuscular CdCl/sub 2/ injections over 13 days followed by an intraperitoneal DMN injection 24 hours later. Untreated and single agent controls were incorporated. One year after DMN exposure, both Series show a significant (p < 0.025) synergistic increase in the incidence of renal neoplasia and an additive increase in the incidence of focal atypical hyperplasia (FAH) of renal tubules. Likewise, there was a synergistic increase in the number of altered foci/areas in livers of Series I animals. In addition, Series I rats with combined treatment had a significant increase in tumor incidence at sites other than kidney. Pretreatment with DMN was more synergistic in toxicity than pretreatment with Cd. Series II animals also showed an apparent shift in renal tumor type from mesenchymal and tubular neoplasms to tubular epithelial neoplasms alone. Theories on the origin(s) of malignant transformation are reviewed as is the biologic important of cadmium in the environment and possible mechanisms of synergistic action. This thesis supports (1) the finding of synergism in the occurrence of renal cancer in man associated with cadmium exposure and cigarette smoking, (2) the importance of synergisms in carcinogenesis, (3) the importance of such interaction in the determination of threshold doses, and (4) the role that indirect mechanisms play in carcinogenic activity of cadmium and other heavy metals.
- Research Organization:
- Boston Univ., MA (USA)
- OSTI ID:
- 6828773
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINES
TOXICITY
CADMIUM
BIOLOGICAL EFFECTS
CARCINOGENESIS
CARCINOGENS
KIDNEYS
RATS
SYNERGISM
TUMOR CELLS
ANIMAL CELLS
ANIMALS
BODY
ELEMENTS
MAMMALS
METALS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology