The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis
Singletary, K; Macdonald, C; Wallig, M
HERO ID
675426
Reference Type
Journal Article
Year
1997
Language
English
PMID
| HERO ID | 675426 |
|---|---|
| In Press | No |
| Year | 1997 |
| Title | The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis |
| Authors | Singletary, K; Macdonald, C; Wallig, M |
| Journal | Carcinogenesis |
| Volume | 18 |
| Issue | 8 |
| Page Numbers | 1669-1673 |
| Abstract | 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. |
| Doi | 10.1093/carcin/18.8.1669 |
| Pmid | 9276647 |
| Wosid | WOS:A1997XQ87800035 |
| Url | https://www.proquest.com/scholarly-journals/plasticizer-benzyl-butyl-phthalate-bbp-inhibits-7/docview/79239279/se-2 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | DNA Adducts; 0; Phthalic Acids; 9,10-Dimethyl-1,2-benzanthracene; 57-97-6; Cytochrome P-450 CYP1A1; EC 1.14.14.1; Glutathione Transferase; EC 2.5.1.18; butylbenzyl phthalate; YPC4PJX59M; Index Medicus; Glutathione Transferase -- metabolism; Animals; Body Weight -- drug effects; Cytochrome P-450 CYP1A1 -- metabolism; Injections, Intraperitoneal; Rats; Female; Liver -- enzymology; Rats, Sprague-Dawley; Mammary Neoplasms, Experimental -- chemically induced; Mammary Glands, Animal -- metabolism; DNA Adducts -- drug effects; DNA Adducts -- analysis; Phthalic Acids -- pharmacology; Mammary Neoplasms, Experimental -- prevention & control; Phthalic Acids -- administration & dosage |
| Is Peer Review | Yes |
| Relationship(s) |
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