Diepoxybutane (DEB)-and mitomycin C (MMC)-associated toxicity was investigated in embryos from the sea urchin (SU) species Sphaerechinus granularis. DEB-and MMC-induced toxicity resulted in S. granularis embryos and larvae at concentrations ranging 10 5 to 10 4 M DEB, and 3 10 3International Atomic Energy Agency, Quai 6 to 3 10 5 M MMC, in terms of larval malformations, developmental arrest and mortality. The formation of DNA oxidative damage, 8-hydroxy-20-deoxyguanosine (8-OHdG) was measured in DEB-and in MMC-exposed embryos (at gastrula stage). A dose-dependent increase in 8-OHdG levels was observed that was significantly correlated with DEB-and MMC-induced developmental defects. The results lend further support to the body of evidence associating both DEB and MMC toxicity with oxidative stress, including DNA oxidative damage. Human & Experimental Toxicology (2001) 20, 651–655.
Korkina LG , Deeva IB , De Biase A , Iaccarino M , Oral R , Warnau M , Pagano G . Redox-dependent toxicity of diepoxybutane and mitomycin C in sea urchin embryo-genesis . Carcinogenesis2000; 21: 213–220 .
2.
Kligerman AD , De Marini DM , Doerr CL , Hanley NM , Milholland VS , Tennant AH . Comparison of cytogenetic effects of 3,4-epoxy-1-butene and 1,2:3,4-die-poxybutane in mouse, rat and human lymphocytes following in vitro G0 exposures . Mutat Res1999; 439: 13–23 .
3.
Henderson RF , Barr EB , Belinsky SA , Benson JM , Hahn FF , Menache MG . 1,3-Butadiene: cancer, mutations, and adducts: Part I. Carcinogenicity of 1,2,3,4-die-poxybutane . Res Rep Health Eff Inst2000; 92: 11–43 .
4.
Pritsos C , Sartorelli AC . Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics . Cancer Res1986; 46: 3528–3532 .
5.
Dusre L , Covey JM , Collins C , Sinha BK . DNA damage, cytotoxicity and free radical formation by mitomycin C in human cells . Chem-Biol Interact1989; 71: 63–78 .
6.
Auerbach AD , Wolman SR . Susceptibility of Fanconi’s anaemia fibroblasts to chromosome damage by carcinogens . Nature1976; 261: 494–496 .
7.
Ishida R , Buchwald M . Susceptibility of Fanconi’s anemia lymphoblasts to DNA cross-linking and alkylating agents . Cancer Res1982; 42: 4000–4006 .
8.
Pagano G . Mitomycin C and diepoxybutane action mechanisms and FANCC protein functions: further insights into the role for oxidative stress in Fanconi’s anaemia phenotype . Carcinogenesis2000; 21: 1067–1068 .
9.
Seaton MJ , Follansbee MH , Bond JA . Oxidation of 1,2-epoxy-3-butene to 1,2:3,4-diepoxybutane by cDNA-expressed human cytochromes P450 2E1 and 3A4 and human, mouse and rat liver microsomes . Carcino-genesis1995; 16: 2287–2293 .
10.
Kemper RA , Krause RJ , Elfarra AA . Metabolism of butadiene monoxide by freshly isolated hepatocytes from mice and rats: different partitioning between oxidative, hydrolytic, and conjugation pathways . Drug Metab Dispos2001; 29: 830–836 .
11.
Suzuki K , Yamamoto W , Park JS , Hanaoka H , Okamoto R , Kirihara Y , Yorishima T , Okamura T , Kumazaki T , Nishiyama M . Regulatory network of mitomycin C action in human colon cancer cells . Jpn J Cancer Res1999; 90: 571–577 .
12.
Belcourt MF , Hodnick WF , Rockwell S , Sartorelli AC . Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH: cytochrome c (P-450) reductase . Proc Natl Acad Sci USA1996; 93: 456–460 .
13.
Graillet C , Pagano G , Girard JP . Stage-specific effects of teratogens on sea urchin embryogenesis . Teratog Carcinog Mutagen1993; 13: 1–14 .
14.
Pagano G , Bonassi S , De Biase A , Degan P , Deeva IB , Doronin YK , Iaccarino M , Oral R , Warnau M , Korkina LG . L-Methionine induces stage-dependent changes of differentiation and oxidative activity in sea urchin embryogenesis . Pharmacol Toxicol1997; 81: 134–143 .
15.
Pagano G , De Biase , Deeva IB , Degan P , Doronin YK , Iaccarino M , Oral R , Trieff NM , Warnau M , Korkina LG . The role of oxidative stress in developmental and reproductive toxicity of tamoxifen . Life Sci2001; 68: 1735–1749 .
16.
Trieff NM , Romaña LA , Esposito A , Oral R , Quiniou F , Iaccarino M , Alcock N , Ramanujam VMS , Pagano G . Effluent from bauxite factory induces developmental and reproductive damage in sea urchins . Arch Environ Contam Toxicol1995; 28: 173–177 .
17.
Warnau M , Iaccarino M , De Biase A , Temara A , Jangoux M , Dubois Ph , Pagano G . Spermiotoxicity and embryotoxicity of heavy metals in the echinoid Paracentrotus lividus . Environ Toxicol Chem1997; 15: 1931–1936 .
18.
Pagano G , Korkina LG , Iaccarino M , De Biase A , Deeva IB , Doronin YK , Guida M , Melluso G , MericS S , Oral R , Trieff NM , Warnau M . Developmental, cytogenetic and biochemical effects of spiked or environmentally polluted sediments in sea urchin bioassays. In Garrigues P , Walker CH , Barth H , (Eds). Biomarkers in marine ecosystems: a practical approach. Amsterdam: Elsevier2001, pp. 85–129.
19.
Fraga CG , Shigenaga MK , Park J-W , Degan P , Ames BN . Oxidative damage to DNA during aging: 8-hydroxy-20-deoxyguanosine in rat organ DNA and urine . Proc Natl Acad Sci USA1990; 87: 4533–4537 .
20.
Floyd RA . The role of 8-hydroguanine in carcino-genesis . Carcinogenesis1990; 9: 1447–1450 .
21.
Wei L , Wei H , Frenkel K . Sensitivity to tumor promotion of SENCAR and C57BL/6J mice correlates with oxidative events and DNA damage . Carcinogenesis1993; 14: 841–847 .
22.
Takeuchi T , Morimoto K . Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi’s anemia patients due to possible catalase deficiency . Carcinogenesis1993; 14: 1115–1120 .
23.
Zunino A , Degan P , Vigo T , Abbondandolo A . Hydrogen peroxide: effects on DNA, chromosomes, cell cycle and apoptosis induction in Fanconi’s anemia cell lines . Mutagenesis2001; 16: 2283–2288 .
24.
Degan P , Bonassi S , De Caterina M , Korkina LG , Pinto L , Scopacasa F , Zatterale A , Calzone R , Pagano G . In vivo accumulation of 8-hydroxy-20-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi’s anaemia families . Carcinogenesis1995; 16: 735–742 .
25.
Pagano G , Cipollaro M , Corsale G , Esposito A , Ragucci E , Giordano GG , Trieff NM . The sea urchin: bioassay for the assessment of damage from environmental contaminants. In Cairns J Jr , (Ed). Community toxicity testing: ASTM STP 920. Philadelphia, PA: American Society for Testing and Materials , 1986, pp. 67–92.
26.
Pagano G , Esposito A , Giordano GG . Fertilization and larval development in sea urchins following exposure of gametes and embryos to cadmium . Arch Environ Contam Toxicol1982; 11: 47–55 .
27.
Pagano G , Esposito A , Bove P , de Angelis M , Rota A , Giordano GG . The effects of hexavalent and trivalent chromium on fertilization and development in sea urchins . Environ Res1983; 30: 442–452 .
28.
Godfrey K . Comparing the means of several groups. In Bailar JC III , Mosteller F , (Eds). Medical uses of statistics. Boston, MA: NEJM Books , 1992, pp. 233–257.
29.
Calabrese EJ , Baldwin LA . Chemical hormesis: its historical foundations as a biological hypothesis . Hum Exp Toxicol2000; 19: 2–31 .
