title: DNA adduct formation and physiological effects from crude oil distillate and its derived base oil in isolated, perfused rat liver.
abstract: A distillate, D431, originating from Venezuelan heavy crude oil and a severely hydro-treated base oil, BO100, derived from this distillate, were tested for DNA adduct formation capacities and overall impact on liver functions. D431 had earlier showed DNA adduct formation in vitro but not in vivo in the rat. In this study, isolated rat liver perfusions were performed to elucidate whether the lack of DNA adducts in vivo was because of lack of uptake or metabolism. The oils were extracted with dimethyl sulfoxide and the extracts added to the perfusion system. Bile production, lactate metabolism and perfusate flow through the organ, which are parameters that reveal the condition of the liver, were continuously monitored. Samples of liver were collected once every hour during perfusion for DNA adduct analysis with (32)P-HPLC. The results for the distillate D431 showed that the production of bile and metabolism of lactate decreased while DNA adduct formation increased with time. The DNA adduct pattern formed in the D431-treated livers was similar to that found earlier in in vitro studies performed on calf thymus DNA (CT-DNA). In the case of DNA adduct formation, virtually no difference with dose was seen, suggesting that perhaps a point of saturation of, for instance, enzymatic systems was reached. The results for base oil BO100 showed no significant difference regarding bile production, lactate metabolism and DNA adduct formation when compared with the control, indicating no toxic or genotoxic activity.
authors.affiliation: Department of Biosciences at Novum, Unit for Analytical Toxicology, Karolinska Institutet, 141 57 Huddinge, Stockholm, Sweden.
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Norén
authors.forename: Magnus
authors.initials: M
authors.lastname: Zeisig
authors.forename: Lars-Gösta
authors.initials: LG
authors.lastname: Ekström
authors.forename: Lennart
authors.initials: L
authors.lastname: Möller
mesh_terms: D000818:Animals; D045424:Complex Mixtures / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010578:Petroleum / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045424:Complex Mixtures; D018736:DNA Adducts; D010578:Petroleum; D019344:Lactic Acid; D004247:DNA