Induction of benzo(a)pyrene metabolism in human mammary epithelial cells by manufactured gas residues

Journal Article · Sat Dec 31 04:00:00 EST 1994 · Environmental and Molecular Mutagenesis

OSTI ID:88813

Goth-Goldstein, R; Levine, G ^[1]; Leadon, S A ^[2]; Chaloupka, K; Safe, S ^[3]

---

1. Lawrence Berkeley Laboratory, CA (United States)
2. Univ. of North Carolina, Chapel Hill, NC (United States)
3. Texas A&M Univ., College Station, TX (United States)

This study was undertaken to evaluate the non-genotoxic effects of manufactured gas plant residues which present complex mixtures of polycyclic aromatic hydrocarbons. The effect of these residues on benzo(a)pyrene (BaP) metabolism in human mammary epithelial cells was studied. Cells were preincubated with hexane-extractable coal tar material for 16 hr, then incubated with {sup 3}H-BaP for 2 hr and the amount of BaP metabolites in cell extracts was determined by HPLC. An up to 5-fold increase over control in BaP metabolites was seen after preincubation with 0.2 {mu}g/ml coal tar material (a oncytotoxic dose). Coal tar extracts were equally effective as pure BaP in inducing BaP metabolism. As BaP constitutes less than 1% of the coal tar, other components in the coal tar mixtures appear to be even more potent than BaP in inducing the enzyme system responsible for BaP metabolism. The increase in BaP metabolites was accompanied by a proportional increase in P4501A1 mRNA as measured by Northern blotting, and resulted in an increase of BaP adducts to DNA. These results show that coal tars and other P450-inducting compounds can act as cocarcinogens by enhancing the genotoxic effects of compounds metabolized by the P4501A1 enzyme.

• OSTI ID: 88813
• Report Number(s): CONF-9405324--
• Journal Information: Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.23 Vol. 23; ISSN 0893-6692; ISSN EMMUEG
• Country of Publication: United States
• Language: English

Related Subjects

10 SYNTHETIC FUELS
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BENZOPYRENE
BIOLOGICAL EFFECTS
COAL TAR
DNA ADDUCTS
EPITHELIUM
GENETIC EFFECTS
MAMMARY GLANDS
MAN
METABOLISM
METABOLITES
POLYCYCLIC AROMATIC HYDROCARBONS
SYNERGISM