Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.1289/ehp.908871· OSTI ID:5624345

Steinberg, P; Schlemper, B; Molitor, E; Platt, K L; Seidel, A; Oesch, F ^[1]

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1. Univ. of Mainz (West Germany)

The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP and DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.

• OSTI ID: 5624345
• Journal Information: Environmental Health Perspectives; (USA), Vol. 88; ISSN 0091-6765
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFLATOXINS
MUTAGEN SCREENING
POLYCYCLIC AROMATIC HYDROCARBONS
REVERTANTS
MUTATION FREQUENCY
TESTOSTERONE
METABOLISM
BENZOPYRENE
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
HYDROXYLATION
LIVER
METABOLITES
MICROSOMES
RATS
SALMONELLA TYPHIMURIUM
ANDROGENS
ANDROSTANES
ANIMAL TISSUES
ANIMALS
ANTIGENS
AROMATICS
BACTERIA
BODY
CELL CONSTITUENTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
GLANDS
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
KETONES
MAMMALS
MATERIALS
MICROORGANISMS
MUTANTS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
RIBOSOMES
RODENTS
SALMONELLA
SCREENING
STEROID HORMONES
STEROIDS
TISSUES
TOXIC MATERIALS
TOXINS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology