Polychlorinated naphthalenes (PCNs) are able to induce cytochrome P-450-dependent microsomal monooxygenase activities in vivo and in vitro. The aim of this study was to investigate the toxicity of a PCN mixture, and its effect on the levels of cytochrome P-450 in rats.
The animals were intragastrically administered a mixture of PCNs in single doses of 250, 500 and 1000 mg/kg b.w. Dissection of animals was performed 24, 72 and 240 hours after administration.
After PCN administration (all doses) the body weight loss (up to 30% in comparison with the control group, 240 hours after administration) and an increase of relative liver mass (about 126 - 153% of controls, 72 hours after administration) were observed.
The exposure to PCN evoked an increase in the level of total cytochrome P-450 as well as the activity of CYP 1A (mediated 7-ethoxyresorufin O-deethylation) at all time points. The maximum activity of CYP 1A (about 12-to 15-fold increase in comparison with the control group) was observed 72 hours after dosing.
Malondialdehyde (MDA), determined in the liver, showed a high increase and 240 hours after administration, the level of MDA was about one order of magnitude greater in comparison with control.
1 Bomman GL , Loganathan BG , Yamashitan N , Seaford K , Sajwan KS . Polychlorinated naphthalenes in pine needles: an atmospheric evaluation of selected locations in the southeastern United States . Organohal Compounds2002; 58: 133–136 .
2.
2 Kannan K , Imagawa T , Blankenship AL , Giesy J.Isomer-specific analysis and toxic evaluation of polychlorinated naphthalenes in soil, sediment and biota collected near the site of a former chlor-alkali plant . Environ Sci Technol1998; 32: 2507–2514 .
3.
3 Kannan K , Yamashita N , Imagawa T , Decoen W , Khim JS , Day RM . Polychlorinated naphthalenes and polychlorinated biphenyls in fishes from Michigan waters including the Great Lakes . Environ Sci Technol2000; 34: 566–572 .
4.
4 Falandysz J.Polychlorinated naphthalenes: an environmental update . Environ Pollut1998; 101: 77–90 .
5.
5 Takasuga T , Inoue T , Ohi E , Ireland P.Development of an all congener specific, HRGC/HRMS analytical method for polychlorinated naphthalenes in environmental samples . Organohal Compounds1994; 19: 177–182 .
6.
6 IPCS (International Programme on Chemical Safety). Chlorinated naphthalenes. Concise International Chemical Assessment Document No. 34. WHO, 2001.
7.
7 EHD . Chloronaphthalene: an environmental-health perspective. Ottawa, Ont.: Department of National Health and Welfare, Environmental Health Directorate , 1982.
8.
8 Elkins HB . The chemistry of industrial toxicology,2nd ed.New York; John B. Wiley & Sons , Inc. 1982.
9.
9 Kimbrough RD , Jensen AA eds. Halogenated biphenyls, naphthalenes, dibenzodioxins and related products. Amsterdam: Elsevier Science Publishers B.V. , 1989.
10.
10 Hayward D.Identification of bioaccumulating polychlorinated naphthalenes and their toxicological significance . Environ Res Sect A1998; 76: 1–18 .
12 US EPAmethod 1613 revision B. Terathrough octachlorinated dioxins and furans by isotope dilution HRGC/HRMS, 1994.
13.
13 Omura T , Sato R.The carbon monoxide-binding pigment of microsomes. I. Evidence for its hemoprotein nature . J Biol Chem1964; 239: 2370–2378 .
14.
14 Guengerich P.Analysis and characterization of enzymes. In Wallace Hayes A ed. Principles and methods of toxicology, third edition. New York: Raven , 1994.
15.
15 Lubert RA , Nims RW , Mayer RT , Cameron JW , Schechtman LM . Measurement of cytochrome P-450 dependent dealkylation of alkoxyphenoxazones in hepatic S9s and hepatocyte homogenates: effects of dicumarol . Mutat Res1985; 142: 127–132 .
16.
16 Kostka G , Palut D , Wiadrowska B.The effect of permetrin and DDT on the activity of cytochrome P450 1A and 2B molecular forms in rat liver . Roez Panstw Zakl Hig1997; 48: 229–237 (in Polish).
18 Uchiyama M , Mihara M.Determination of malonalde hyde precursor in tissue by thiobarbituric acid test . Anal Biochem1978; 86: 271–278 .
19.
19 Sedlak T , Lindsay RH . Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmans reagent . Anal Biochem1968; 25: 192–205 .
20.
20 Poznanska E , Osinski T.A modification of the colorimetric method of aminotransferases determination in blood serum . Diagn Lab1968; 4: 349–353 (in Polish).
21.
21 Richterich R.Clinical chemistry. Theory and practice. Warsaw: PZWL , 1971 (in Polish).
22.
22 Wilkinson L.SYSTAT: the system for statistic. Evanston, IL: Systat, Inc. , 1990.
23.
23 Witt K , Niessen KH . Toxaphenes and chlorinated naphthalenes in adipose tissue of children . J Pediat Gastroenterol Nutr2000; 39: 164–169 .
24.
24 McConnell EE . Acute and chronic toxicity and carcinogenesis in animals. In Kimbrough RD , Jensen AA eds. Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division), 1989: 161–193.
25.
25 Mäntylä E , Ahotupa M.Polychlorinated biphenyls and naphthalenes: long-lasting induction of oxidative stress in the rat . Chemosphere1993; 27: 383–390 .
26.
26 Wagstaff DJ . Effects of chlorinated naphthalenes on liver levels of detoxication enzymes and vitamin A . Toxicol Appl Pharmacol1973; 25: 490–491 .
27.
27 Ahotupa M , Aitio A.Effect of chlorinated naphthalenes and terphenyls on the activities of drug metabolizing enzymes in rat liver . Biochem Biophys Res Commun1980; 93: 250–257 .
28.
28 Campbell MA , Bandiera S , Robertson L , Parkinson A , Safe S.Octachloronaphthalene induction of hepatic microsomal aryl hydrocarbon hydroxylase activity in the immature male rat . Toxicology1981; 22: 123–132 .
29.
29 Campbell MA , Bandiera S , Robertson L , Parkinson A.Hepta-, hexa-, tetra-, and dichloronaphthalene congeners as inducers of hepatic microsomal drug-metabolizing enzymes . Toxicology1983; 26: 193–205 .
30.
30 Safe S , Robertson S , Parkinson A , Shilling M , Cockerline RC . Polybrominated biphenyls, polychlorinated naphthalenes and polychlorinated terphenyls as microsomal enzyme inducers. In Khan MAQ ed. Toxicology of halogenated hydrocarbons: health and ecological effects. New York, NY: American Chemical Society, Environmental Chemistry Division , 1981.
31.
31 Hanberg A , Wærn F , Asplund L , Haglund E , Safe S.Swedish dioxin survey: determination of 2,3,7,8-TCDD toxic equivalent factors for some polychlorinated biphenyls and naphthalenes using biological tests . Chemosphere1990; 20: 1161–1164 .
32.
32 Hanberg A , Stahlberg M , Georgellis A , deWit C , Ahlborg UG . Swedish dioxin survey: evaluation of the H-4-II E bioassay for screening environmental samples for dioxin-like enzyme induction . Pharmacol Toxicol1991; 69: 442–449 .
33.
33 Engwall M , Brunström B , Jakobsson E.EROD and AHH-inducing potency and lethality of chlorinated naphthalenes in chicken (Gallus domesticus) and eider duck (Somateria mollissima) embryos . Organohal Compounds1993; 14: 151–154 .
34.
34 Engwall M , Brundström B , Jakobsson E.Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH)-inducing potency and lethality of chlorinated naphthalenes in chicken (Gallus domesticus) and eider duck (Somateria mollissima) embryos . Arch Toxicol1994; 68: 37–42 .
35.
35 Brunström B , Engwall M , Hjelm K , Lindqvist L , Zebuhr Y.EROD induction in cultured chick embryo liver: a sensitive bioassay for dioxin-like environmental pollutants . Environ Toxicol Chem1995; 14: 837–842 .
36.
36 Soucek P , Gut I.Cytochromes P-450 in rats: structures, functions, properties and relevant human forms . Xenobiotica1992; 22: 83–103 .
37.
37 DeBethizy JD , Hayes JR . Metabolism: a determinant of toxicity. In Hayes JR ed. Principles and methods of toxicology. New York: Raven Press , 1989.
38.
38 Uno S , Dalton TP , Derkenne S , Curran CP , Miller ML , Shertzer HG et al. Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P-450 is more important than metabolic activation . Mol Pharmacol2004; 65: 1225–1237 .
39.
39 Klasson-Wehler E , Jakobsson E , Orn U.Metabolism of polychlorinated naphthalenes and a tetrabrominated diphenyl ether . Organohal Compounds1996; 28: 495–499 .
40.
40 Cockerline R , Schilling M , Safe S.Polychlorinated naphthalenes as hepatic microsomal enzyme inducers in the immature male rat . Gen Pharmacol1981; 12: 83–87 .
41.
41 Ohguma K.Experimental study of polychlorinated naphthalene (PCN) intoxication: II. Changes in oxidative phosphorylation of liver mitochondria, and in TBA and ATP of the liver . Okayama Igakkai Zasshi1979; 910: 1461–1466 .
