1,2-Dichloroethane has been consistently demonstrated to be genotoxic
in numerous in vitro and in vivo assays for a wide range of end-points. It has been mutagenic in Salmonella typhimurium, especially in the presence of an exogenous activation system (Milman et al., 1988; Barber et al., 1981; Moriya et al., 1983 ) , and induces unscheduled DNA synthesis (Williams et al., 1989; Milman et al., 1988), induces gene mutation (,Tan & Hsie, 1981) and forms adducts
with DNA in mammalian cells in vitro (Banerjee, 1988). It binds to DNA in all reported in vivo studies in rats and mice (Prodi et al., 1986). 1,2-Dichloroethane has also induced somatic cell and sex-linked
recessive lethal mutations in Drosophila (Nylander et al., 1978; Kramers et al., 1991). Available data on genotoxicity are consistent with the hypothesis that the glutathione pathway of conjugation (i.e. production of the glutathione episulfonium ion) is probably of greater
significance than the P-450 pathway as the major route for DNA damage (Guengerich et al., 1980; Rannug, 1980; Sundheimer et al., 1982; Inskeep et al., 1986; Koga et al., 1986; Simula et al., 1993); mutation frequency in human cell lines has been correlated with
variations in levels of glutathione- S-transferase activities (Crespi et al., 1985).
References
EBanerjee S (1988) DNA damage in rodent liver by 1,2-dichloroethane, a hepatocarcinogen. Cancer biochemistry and biophysics, 10:165-173.
EBarber RD, Donish WH, Mueller KR (1981) A procedure for the quantitative
measurement of the mutagenicity of volatile liquids in the Ames Salmonella microsome assay. Mutation research,
90:31-48.
ECrespi CL, Seixas GM, Turner TR, Ryan CG, Penman BW (1985) Mutagenicity
of 1,2-dichloroethane and 1,2-dibromoethane in two human lymphoblastoid
cell lines. Mutation research,
142:133-140.
EGuengerich FP, Crawford WM, Domoradzki JY, MacDonald TL, Watanabe PG
(1980) In vitro activation of 1,2-dichloroethane by
microsomal and cytosolic enzyme. Toxicology and applied pharmacology, 55:303-317.
EInskeep PB, Koga N, Cmarik JL, Guengerich FP (1986) Covalent binding
of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct, S-[2[(N7-guanyl)ethyl]glutathione. Cancer research, 46:2839-2844.
EKoga N, Inskeep PB, Harris TM, Guengerich FP (1986) S-[2-(N7-guanyl)ethyl] glutathione, the major DNA
adduct formed from 1,2-dibromoethane. Biochemistry, 25:2192-2198.
K
EKramers PG, Mout HC, Bissumbhar B, Mulder CR (1991) Inhalation exposure in Drosophila mutagenesis assays: experiments with
aliphatic halogenated hydrocarbons, with emphasis on the genetic
activity profile of 1,2-dichloroethane. Mutation research,
252:17-33.
EMilman HA, Storey DL, Riccio ES, Sivak A, Tu AS, Williams GM, Tong C,
Tyson CA (1988) Rat liver foci and in vitro assays to
detect initiating and promoting effects of chlorinated ethanes
and ethylenes. Annals of the New York Academy of Sciences,
534:521-530.
EMoriya M, Ohta T, Watanabe K, Miyazawa T, Kato K, Shirasu Y (1983) Further
mutagenicity studies on pesticides in bacterial reversion assay systems.
Mutation research, 116:185-216.
ENylander P-O, Olofsson H, Rasmuson B, Svahlin H (1978) Mutagenic effects
of petrol in Drosophila melanogaster. I. Effects of
benzene and 1,2-dichloroethane. Mutation research, 57:163-167.
EProdi G, Arfelini G, Colacci A, Grilli S, Mazzulo M (1986) Interaction
of halocompounds with nucleic acids. Toxicologic pathology, 14:438-444.
ERannug U (1980) Genotoxic effects of 1,2-dibromoethane and 1,2-dichloroethane.
Mutation research, 76:269-295.
ESimula TP, Glancey MG, Wolf CR (1993) Human glutathione S-transferase-expressing Salmonella typhimurium tester
strains to study the activation/detoxification of mutagenic
compounds: studies with halogenated compounds, aromatic amines
and aflatoxin B1. Carcinogenesis, 14:1371-1376.
ESundheimer DW, White RD, Brendel K, Sipes IC (1982) The bioactivation
of 1,2-dibromoethane in rat hepatocytes: covalent binding to nucleic acids.
Carcinogenesis, 3:1129-1133.
ETan E-L, Hsie AW (1981) Mutagenicity and cytotoxicity of haloethanes
as studied in the CHO/HGPRT system. Mutation research, 90:183-191.
EWilliams GM, Mori H, McQueen CA (1989) Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals. Mutation research, 221:263-286.
|