Styrene oxide-induced HPRT mutations, DNA adducts and DNA strand breaks in cultured human lymphocytes.
Styrene-7,8-oxide (SO) is the major in vivo metabolite of styrene, a widely used plastic monomer. SO has been classified as probably carcinogenic to humans. We studied the genotoxic effects of SO in human peripheral blood lymphocytes (PBL) in vitro. SO-treatment in the range of 0.05-0.6 mM for 24 h resulted in a dose-dependent decrease of cell survival and increase of HPRT mutation, O6-guanine DNA adducts and DNA strand breaks, whereas higher concentrations caused pronounced cell death. SO was a weak mutagen, inducing at most 10-20 mutants per 10(6) clonable cells (approximately 4-fold over the background) after treatment with 0.2-0.4 mM for 24 h or 6 days. The levels of DNA adducts in treated cells correlated with SO-concentrations, but only four adducts per 10(8) nucleotides were detected at the highest treatment concentrations. Yet, adducts were still detectable in cells that had been cultured for 6-8 days after treatment. SO-induced DNA strand breaks, measured with the Comet assay, were detectable after 1 h exposure to 0.05-0.1 mM. Post-treatment incubation for 24 h decreased the level of DNA strand breaks to the control level. There was no correlation between the levels of DNA adducts and frequency of HPRT mutation. The present results indicate that SO is relatively inefficient in inducing HPRT mutation and O6-guanine DNA adducts in human lymphocytes in vitro, which may be related to its pronounced cytotoxicity at concentrations above 0.4 mM. A comparison with previous in vivo data obtained by the same assays in T-lymphocytes of styrene-exposed workers suggests that chronic, low dose exposure to styrene in the work environment may be more efficient in inducing persistent DNA adducts and HPRT mutation than acute, short-term exposure.
Bastlová
T
T
Center for Nutrition and Toxicology, Karolinska Institute, Huddinge, Sweden.
Vodicka
P
P
Peterková
K
K
Hemminki
K
K
Lambert
B
B
D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D018736:DNA Adducts; D004852:Epoxy Compounds; D009153:Mutagens; D004247:DNA; C013690:styrene oxide; D007041:Hypoxanthine Phosphoribosyltransferase