THE PLASTICIZER BENZYL BUTYL PHTHALATE (BBP) INHIBITS 7,12-DIMETHYLBENZ[A]ANTHRACENE (DMBA)-INDUCED RAT MAMMARY DNA ADDUCT FORMATION AND TUMORIGENESIS

Although the risk for cancer is multifactorial, a substantial portion of cancer incidence rates is related to environmental factors, includi ng diet and environmental chemicals, The magnitude of the contribution to cancer of the breast from exposure to environmental chemicals rema ins unclear, The phthalate ester plasticizers are abundantly-produced industrial chemicals that have become widely-dispersed environmental p ollutants, The present studies were conducted to determine the effect of the phthalate ester, benzyl butyl phthalate (BBP) on mammary gland carcinogenesis induced in the female rat by the polycyclic aromatic hy drocarbon (PAH) 7,12-dimethylbenz[a]anthracene (DMBA), Exposure to BBP (i.p. injection) at 100 and 500 mg/kg doses for 5 days resulted in a significant 72 and 92% inhibition, respectively, in the in vivo format ion of mammary DMBA-DNA adducts, compared to controls, Treatment with BBP (i.g. intubation) for 7 days resulted in a significant (48%) inhib ition in mammary DMBA-DNA adduct formation only for those animals rece iving the 500 mg/kg dose, compared to controls, Administration of BBP (i.g.) at 500 mg/kg for 7 days also was associated with a significant 8.5-fold increase in the liver activity of 7-ethoxyresorufin-O-deethyl ase. No change in liver glutathione-S-transferase activity was observe d for animals treated with both BBP (i.g.) doses, Treatment with BBP ( i.g.) at 250 and 500 mg/kg doses for 7 days prior to DMBA administrati on resulted in a significant 37% decrease in mammary tumor incidence f or both doses, compared to controls, The number of mammary adenocarcin omas per rat was significantly inhibited by 60 and 70% for rats expose d to BBP at the 250 and 500 mg/kg doses, respectively, compared to con trols, Therefore, the present studies indicate that BBP acts as a bloc king agent toward DMBA-induced rat mammary DNA adduct formation and ma mmary carcinogenesis. This effect partly may be due to increased metab olism of BBP in the liver, These results underscore the need to furthe r examine the effect of BBP and other phthalates on the various stages of mammary carcinogenesis, as web as on the metabolism of mammary car cinogens.