Analysis of cytogenetic effects and DNA adduct formation induced by safrole in Chinese hamster lung cells.
Safrole (1-allyl-3,4-methylenedioxybenzene) was tested for its ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) and to form DNA adducts in Chinese hamster lung (CHL) cells, in order to investigate the relationship between cytogenetic effects and DNA adduct formation under the same treatment conditions. The cells were treated with 0.025-0.2 mg/ml safrole in the presence or absence of rat liver postmitochondrial supernatant fraction (S9). Safrole induced significant SCEs and CAs dose-dependently in the presence of S9. SCEs ranged in number from 15.6 to 21.1 SCEs/cell and CAs were observed in 4-37% of cells. Using the 32P-postlabeling assay, two major and two minor safrole-DNA adducts were detected in DNA digests obtained from CHL cells in the presence of S9. The levels of total DNA adducts ranged from 1.3 to 22.8 adducts/10(7) nucleotides. The two major adducts were shown to be guanine derivatives since these adducts comigrated on polyethylenimine plates with the adducts produced by the reaction of safrole with 2'-deoxyguanosine 3'-monophosphate. A correlation was seen between DNA adducts and SCEs or CAs. Neither induction of SCEs and CAs nor formation of DNA adducts was observed in the absence of S9. These findings suggest that SCEs and CAs induced by safrole result from covalent DNA modification metabolically activated by S9 in cultured cells.
Daimon
H
H
Drug Safety Research Laboratories, Eisai Co., Ltd., Gifu-ken, Japan.
Sawada
S
S
Asakura
S
S
Sagami
F
F
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007553:Isotope Labeling; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008647:Mesocricetus; D009152:Mutagenicity Tests; D010761:Phosphorus Radioisotopes; D012451:Safrole / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D012451:Safrole