Cytotoxic and genotoxic effects of fumonisin B1 on rabbit kidney RK13 cell line

被引:36
作者
Rumora, L
Kovacic, S
Rozgaj, R
Cepelak, I
Pepeljnjak, S
Grubisic, TZ
机构
[1] Univ Zagreb, Fac Pharm & Biochem, Dept Med Biochem & Haematol, Zagreb 10000, Croatia
[2] Fac Pharm & Biochem, Dept Microbiol, Zagreb 10000, Croatia
[3] Inst Med Res & Occupat Hlth, Mutagenesis Unit, Zagreb 10000, Croatia
关键词
fumonisin B1; apoptosis; micronucleus assay; RK13; cells;
D O I
10.1007/s00204-001-0304-8
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Fumonisins, mycotoxins produced by certain strains of Fusarium moniliforme, could induce various diseases in animals and are suspected human carcinogens. Fumonisin B-1 (FB1), the most commonly found fumonisin, has been characterised as a tumour initiator and a tumour promoter, a mitogen and an anti-proliferative agent. In this study we examined the cytotoxicity and genotoxicity of FB1 in rabbit kidney RK13 cells. To evaluate the effects of FB1 on survival of this cell line we analysed cell viability, membrane integrity, DNA fragmentation and overall morphology of the cells. The genotoxic potential of FB1 was estimated by monitoring the ability of this mycotoxin to induce micronuclei in RK13 cells. Exposure to FB1 caused a significant increase in micronucleus frequency in a concentration- and in a time-dependent manner. Nanomolar concentrations of FB1 decreased cell viability after 24 h and even more so after 48 h of exposure. The morphological changes observed suggested that an increased number of RK13 cells were dying by the process of apoptosis. However, FB1 also induced impairments of cell and mitochondrial membrane integrity, as assessed by lactate dehydrogenase and glutamate dehydrogenase leakage. These results could imply that nanomolar concentrations of FB1 induced apoptosis, which subsequently may proceed to secondary necrosis. In summary, our observations suggest that FB1 is genotoxic and cytotoxic to RK13 cells.
引用
收藏
页码:55 / 61
页数:7
相关论文
共 49 条
[1]   Cytotoxicity of fumonisin B1:: implication of lipid peroxidation and inhibition of protein and DNA syntheses [J].
Abado-Becognee, K ;
Mobio, TA ;
Ennamany, R ;
Fleurat-Lessard, F ;
Shier, WT ;
Badria, F ;
Creppy, EE .
ARCHIVES OF TOXICOLOGY, 1998, 72 (04) :233-236
[2]  
Bondy G, 1996, ADV EXP MED BIOL, V392, P251
[3]   THE ROLE OF DNA FRAGMENTATION IN APOPTOSIS [J].
BORTNER, CD ;
OLDENBURG, NBE ;
CIDLOWSKI, JA .
TRENDS IN CELL BIOLOGY, 1995, 5 (01) :21-26
[4]   Renal effects of fumonisin mycotoxins in animals [J].
Bucci, TJ ;
Howard, PC ;
Tolleson, WH ;
Laborde, JB ;
Hansen, DK .
TOXICOLOGIC PATHOLOGY, 1998, 26 (01) :160-164
[5]   Effect of fumonisin mycotoxins in animals [J].
Bucci, TJ ;
Howard, PC .
JOURNAL OF TOXICOLOGY-TOXIN REVIEWS, 1996, 15 (03) :293-302
[6]  
Caria H, 1996, TERATOGEN CARCIN MUT, V16, P243, DOI 10.1002/(SICI)1520-6866(1996)16:5<243::AID-TCM1>3.0.CO
[7]  
2-I
[8]   A MUTAGENIC METABOLITE PRODUCED BY FUSARIUM-MONILIFORME ISOLATED FROM LINXIAN COUNTY, CHINA [J].
CHENG, SJ ;
JIANG, YZ ;
LI, MH ;
LO, HZ .
CARCINOGENESIS, 1985, 6 (06) :903-905
[9]   Fumonisin B1, a mycotoxin contaminant of cereal grains, and inducer of apoptosis via the tumour necrosis factor pathway and caspase activation [J].
Ciacci-Zanella, JR ;
Jones, C .
FOOD AND CHEMICAL TOXICOLOGY, 1999, 37 (07) :703-712
[10]   KEY MORPHOLOGICAL FEATURES OF APOPTOSIS MAY OCCUR IN THE ABSENCE OF INTERNUCLEOSOMAL DNA FRAGMENTATION [J].
COHEN, GM ;
SUN, XM ;
SNOWDEN, RT ;
DINSDALE, D ;
SKILLETER, DN .
BIOCHEMICAL JOURNAL, 1992, 286 :331-334