Abstract
The synthetic pyrethroids cypermethrin, deltamethrin, fenvalerate, permethrin, and the fenvalerate metabolite p-chlorophenylisovaleric acid were investigated for inhibition of gap-junctional intercellular communication in vitro in the Chinese hamster lung fibroblast (V79) metabolic cooperation assay. Fenvalerate was furthermore studied for enhancement of gamma-glutamyl transpeptidase-positive enzyme altered foci incidence in partially hepatectomized, nitrosodiethylamine-initiated male Sprague Dawley rats. The in vitro studies showed that fenvalerate and p-chlorophenylisovaleric acid were inhibitors of intercellular communication at non-cytotoxic concentrations while cypermethrin, deltamethrin, and permethrin were inactive. In the in vivo study in rat liver, fenvalerate administered p.o. (75 mg/kg/day) 5 days a week for 10 weeks induced significantly more foci per cm3 and a larger percentage of liver tissue occupied by foci tissue compared to a vehicle control group. Analysis of size distributions of foci in fenvalerate- and vehicle-treated rats showed elevated foci incidences in fenvalerate-treated rats at all foci sizes. Fenvalerate induced no hepatotoxic effects as judged by plasma transaminase activities and histopathology. The results of this study suggest fenvalerate to be a potential tumour promoter.
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References
Amer SM, Aboul-ela EI (1985) Cytogenetic effects of pesticides III. Induction of micronuclei in mouse bone marrow by the insecticides cypermethrin and rotenone. Mutat Res 155: 135–142
Ashendel CL (1985) The phorbol ester receptor: a phospholipid-regulated protein kinase. Biochim Biophys Acta 822: 219–242
Beeman RW (1982) Recent advances in mode of action of insecticides. Ann Rev Entomol 27: 253–281
Campbell HA, Pitot HC, Potter VR, Laishes BA (1982) Application of quantitative stereology to the evaluation of enzyme-altered foci in rat liver. Cancer Res 42: 465–472
Campbell HA, Yuan-Ding Xu, Hanigan MH, Pitot HC (1986) Application of quantitative stereology to the evaluation of phenotypically heterogeneous enzyme-altered foci in the rat liver. J Natl Cancer Inst 76: 751–767
Carlson GP, Schoening GP (1980) Induction of liver microsomal NADPH cytochrome c reductase and cytochrome P-450 by some new synthetic pyrethroids. Toxicol Appl Pharmacol 52: 507–512
Chatterjee KK, Talukder G, Sharma A (1982) Effects of synthetic pyrethroids on mammalian chromosomes. Mutat Res 105: 101–106
Davidson JS, Baumgarten IM, Harley EH (1985a) Use of a new citrulline incorporation assay to investigate inhibition of intercellular communication by 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. Cancer Res 45: 515–519
Davidson JS, Baumgarten IM, Harley EH (1985b) Inhibition of intercellular junctional communication in human fibroblasts by triphenylmethane, triphenylmethylchloride, tetraphenylboron and related compounds. Biochim Biophys Acta 847: 1–7
Enomoto T, Martel N, Kanno Y, Yamasaki H (1984) Inhibition of cell-cell communication between BALB/c 3T3 cells by tumor promoters and protection by cAMP. J Cell Physiol 121: 323–333
FAO/WHO (1980) 1979 Evaluations of some pesticide residues in food. Rome, Food and Agriculture Organization of the United Nations (FAO Plant production and Protection Paper 20 Suppl)
FAO/WHO (1981) 1980 Evaluations of some pesticide residues in food, Rome, Food and Agriculture Organization of the United Nations (FAO Plant production and Protection Paper 26 Suppl)
Goldfarb S, Pugh TD (1986) Multistage rodent hepatocarcinogenesis. Prog Liver Dis VIII: 597–620
Hagmann J (1982) Inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by the insecticide DDT. FEBS Lett 143: 52–54
Higgins GM, Anderson RM (1931) Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12: 186–202
Jones OT, Lee AG (1986) Effects of pyrethroids on the activity of a purified (Ca2+ -Mg2+)-ATPase. Pestic Biochem Physiol 25: 420–430
Leonard TB, Adams T, Popp JA (1986) Dinitrotoluene isomer-specific enhancement of the expression of diethylnitrosamine-initiated hepatocyte foci. Carcinogenesis 7: 1797–1803
Loewenstein WR (1981) Junctional intercellular communication. The cell-to-cell membrane channel. Physiol Rev 61: 829–913
L'vova TS (1984) Mutagenic action of 5 prospective pesticides on mouse bone marrow, in a culture of human peripheral blood lymphocytes and on saccharomycete yeasts. Tsitol Genet 18: 455–457
Madhukar BV, Yoneyama M, Matsumura F, Trosko JE, Tsushimoto G (1983) Alteration of calcium transport by tumor protomoters, 12-0-tetradecanoyl phorbol-13-acetate and p,p′-dichlorodiphenyltrichloroethane, in the Chinese hamster V79 fibroblast cell line. Cancer Lett 18: 251–259
Nychka D, Pugh TD, King JH, Koen H, Wahba G, Chover J, Goldfarb S (1984) Optimal use of sampled tissue sections for estimating the number of hepatocellular foci. Cancer Res 44: 178–183
Ohkawa H, Kaneko H, Tsujio H, Miyamoto J (1979) Metabolism of fenvalerate (Sumicidin) in rats. J Pestic Sci 4: 143–155
Parker CM, McCullough CB, Gellatly JBM, Johnston CD (1983) Toxicologic and carcinogenic evaluation of fenvalerate in the B6C3F1 mouse. Fundam Appl Toxicol 3: 114–120
Parker CM, Patterson DR, Van Gelder GA, Gordon EB, Valerio MG, Hall WC (1984) Chronic toxicity and carcinogenicity evaluation of fenvalerate in rats. J Toxicol Environ Health 13: 83–97
Parker CM, Albert JR, Van Gelder GA, Patterson DR, Taylor JL (1985) Neuropharmacologic and neuropathologic effect of fenvalerate in mice and rats. Fundam Appl Toxicol 5: 278–286
Pilot HC, Barsness L, Goldsworthy T (1978) Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271: 456–457
Pluijmen M, Drevon C, Montesano R, Malaveille C, Hautefeuille A, Bartsch H (1984) Lack of mutagenicity of synthetic pyrethroids in Salmonella typhimurium strains and in V79 Chinese hamster cells. Mutat Res 137: 7–15
Pugh TD, King HJ, Koen H, Nychka D, Chover J, Wahba G, He Y, Goldfarb S (1983) Reliable stereological method for estimating the number of microscopic hepatocellular foci from their transections. Cancer Res 43: 1261–1268
Rashatwar SS, Matsumura F (1985) Interaction of DDT and pyrethroids with calmodulin and its significance in the expression of enzyme activities of phosphodiesterase. Biochem Pharmacol 34: 1689–1694
Remandet B, Gouy D, Berthe J, Mazue G, Williams GM (1984) Lack of initiating or promoting activity of six benzodiazepine tranquilizers in rat liver limited bioassays monitored by histopathology and assay of liver and plasma enzymes. Fundam Appl Toxicol 4: 152–163
Rutenburg AM, Kim H, Fishbein JW, Hanker JS, Wasserkrug HL, Seligman AM (1969) Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity. J Histochem Cytochem 17: 517–526
Ruzo LO, Casida JE (1977) Metabolism and toxicology of pyrethroids with dihalovinyl substituents. Environ Health Perspect 21: 265–292
Schulte-Hermann R (1979) Adaptive liver growth induced by xenobiotic compounds: Its nature and mechanism. Arch Toxicol Suppl 2: 113–124
Schulte-Hermann R (1985) Tumor promotion in the liver. Arch Toxicol 57: 147–158
Sokal RR, Rohlf FJ (1981) Biometry — The principles and practice of statistics in biological research, 2nd Ed. WH Freeman, San Francisco, pp 242–262
Telang S, Tong C, Williams GM (1982) Epigenetic membrane effects of a possible tumor promoting type on cultured liver cells by the non-genotoxic organochlorine pesticides chlordane and heptachlor. Carcinogenesis 3: 1175–1178
Trosko JE, Chang CC (1984) Role of intercellular communication in tumor promotion. In: Slage TJ (ed) Cellular Responses to tumor promoters. Mechanism of tumor promotion. Vol 4: Cellular responses to tumor promoters. CRC Press, Boca Raton, FL, pp 119–145
Trosko JE, Yotti LP, Dawson B, Chang CC (1981) In vitro assays for tumor promoters. In: Stich HF, San RHC (eds) Short-term tests for chemical carcinogens. Springer-Verlag, Berlin Heidelberg New York, pp 420–427
Trosko JE, Yotti LP, Warren ST, Tsushimoto G, Chang CC (1982) Inhibition of cell-cell communication by tumor promoters. Carcinogen Compr Surv 7: 565–585
Trosko JE, Jone CM, Rintel RA, Chang CC (1985) Potential role of calmodulin in tumor promotion: Modulation of gap junctional intercellular communication. In: Hidaka H, Hartshorne DJ (eds) Calmodulin antagonists and cellular physiology. Academic Press, New York, pp 99–115
Tsushimoto G, Trosko JE, Chang CC, Aust SD (1982) Inhibition of metabolic cooperation in Chinese hamster V79 cells in culture by various polybrominated biphenyl (PBB) congeners. Carcinogenesis 3: 181–185
Williams GM (1981) Liver carcinogenesis. The role for some chemicals of an epigenetic mechanism of liver-tumourpromotion involving modification of the cell membrane. Food Cosmet Toxicol 19: 577–583
Williams GM, Telang S, Tong C (1981) Inhibition of intercellular communication between liver cells by the liver tumour promoter 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. Cancer Lett 11: 339–344
Wärngård L, Flodström S, Ljungquist S, Ahlborg U (1985) Inhibition of metabolic cooperation in Chinese hamster lung fibroblast cells (V79) in culture by various DDT-analogs. Arch Environ Contam Toxicol 14: 541–546
Wärngård L, Flodström S, Ljungquist S, Ahlborg UG (1987) Interaction between quercetin, TPA and DDT in the V79 metabolic cooperation assay. Carcinogenesis 8: 1201–1208
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Flodström, S., Wärngård, L., Ljungquist, S. et al. Inhibition of metabolic cooperation in vitro and enhancement of enzyme altered foci incidence in rat liver by the pyrethroid insecticide fenvalerate. Arch Toxicol 61, 218–223 (1988). https://doi.org/10.1007/BF00316637
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DOI: https://doi.org/10.1007/BF00316637