Relationships between cellular superoxide dismutase and susceptibility to chemically induced cancer in the rat mammary gland

Increasing evidence suggests a role for reactive free radicaloxygen species in the multi-stage events of chemical carcino-genesis.We hypothesized that variations in the level of super-oxidedismutase (SOD), a major endogenous antioxidant enzyme, mayaccount in part for variations in susceptibility to cancer inducedby polycyclic aromatic hydrocarbons (PAH). The SOD activityof mammary epithelial cells from rats with varying susceptibilityto dimethylbenz[a]anthracene (DMBA)-induced breast cancer wasassayed. Ageing, pregnancy and previous multiple pregnanciesreduce susceptibility of Sprague Dawley female rats to DMBA.These decreases in susceptibility were correlated with increasedlevels of SOD activity. Only minor differences in SOD activitywas observed in mammary epithelium of genetic strains of ratswith differences in susceptibility to DMBA. These data suggestthat, in models where physiological differences may accountfor variations in effectiveness of PAH to induce mammary cancer,SOD activity is inversely correlated with breast cancer susceptibilityand support the hypothesis that cancer susceptibility may bepartially mediated through reactive free radical oxygen intermediates.