Carcinogenesis, Vol 18, 1669-1673, Copyright © 1997 by Oxford University Press
K Singletary, C MacDonald and M Wallig
Although the risk for cancer is multifactorial, a substantial portion of
cancer incidence rates is related to environmental factors, including diet
and environmental chemicals. The magnitude of the contribution to cancer of
the breast from exposure to environmental chemicals remains unclear. The
phthalate ester plasticizers are abundantly-produced industrial chemicals
that have become widely- dispersed environmental pollutants. 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 hydrocarbon (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 formation of mammary DMBA-DNA
adducts, compared to controls. Treatment with BBP (i.g. intubation) for 7
days resulted in a significant (48%) inhibition in mammary DMBA-DNA adduct
formation only for those animals receiving 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-deethylase. No change in liver glutathione-S-
transferase activity was observed 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 administration resulted in a significant 37% decrease in
mammary tumor incidence for both doses, compared to controls. The number of
mammary adenocarcinomas per rat was significantly inhibited by 60 and 70%
for rats exposed to BBP at the 250 and 500 mg/kg doses, respectively,
compared to controls. Therefore, the present studies indicate that BBP acts
as a blocking agent toward DMBA-induced rat mammary DNA adduct formation
and mammary carcinogenesis. This effect partly may be due to increased
metabolism of BBP in the liver. These results underscore the need to
further examine the effect of BBP and other phthalates on the various
stages of mammary carcinogenesis, as well as on the metabolism of mammary
carcinogens.
ARTICLES
The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12- dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis
Department of Food Science and Human Nutrition, University of Illinois, Urbana 61801, USA.
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