Abstract
The capability of covalent binding to DNA to predict the initiating potential of chemical carcinogens was compared for the assays performed in vivo (rodent liver DNA) and in vitro (purified DNA incubated in the presence of mouse and rat liver microsomes). A quantitative correlation between DNA adducts and carcinogenic potency was investigated. The in vivo assay appeared slightly, but not significantly, more predictive than the in vitro assay. Also predictivity was slightly higher both in vivo and in vitro when we referred to liver carcinogenicity instead of overall carcinogenicity. The predictive ability found for DNA covalent binding (both in vivo and in vitro) was similar to that of many short-term tests (such as mutagenicity, DNA damage/repair, SCEs, and cell transformation tests). The covalent DNA binding, measured after incubation with DNA in vitro in the presence of liver microsomes, could therefore be a reasonable short-term test offering greater rapidity of execution and requiring the sacrifice of fewer animals than the corresponding in vivo test.
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Selected References
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- Alexandrov K., Frayssinet C. Microsome-dependent binding of benzo(alpha)pyrene and aflatoxin B1 to DNA, and benzo(alpha)pyrene binding to aflatoxin-conjugated DNA. Cancer Res. 1974 Dec;34(12):3289–3295. [PubMed] [Google Scholar]
- Allen L. M., Creaven P. J. Effect of microsomal activation on interaction between isophosphamide and DNA. J Pharm Sci. 1972 Dec;61(12):2009–2011. doi: 10.1002/jps.2600611232. [DOI] [PubMed] [Google Scholar]
- Arfellini G., Bartoli S., Colacci A., Mazzullo M., Galli M. C., Prodi G., Grilli S. In vivo and in vitro binding of 1,2-dibromoethane and 1,2-dichloroethane to macromolecules in rat and mouse organs. J Cancer Res Clin Oncol. 1984;108(2):204–213. doi: 10.1007/BF00402468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arfellini G., Grilli S., Colacci A., Mazzullo M., Prodi G. In vivo and in vitro binding of benzene to nucleic acids and proteins of various rat and mouse organs. Cancer Lett. 1985 Sep 15;28(2):159–168. doi: 10.1016/0304-3835(85)90071-0. [DOI] [PubMed] [Google Scholar]
- Ashurst S. W., Cohen G. M. A benzo[alpha]pyrene-7,8-dihydrodiol-9,10-epoxide is the major metabolite involved in the binding of benzo[alpha]pyrene to DNA in isolated viable rat hepatocytes. Chem Biol Interact. 1980 Jan;29(1):117–127. doi: 10.1016/0009-2797(80)90091-5. [DOI] [PubMed] [Google Scholar]
- Banerjee S., Van Duuren B. L. Binding of carcinogenic halogenated hydrocarbons to cell macromolecules. J Natl Cancer Inst. 1979 Sep;63(3):707–711. doi: 10.1093/jnci/63.3.707. [DOI] [PubMed] [Google Scholar]
- Banerjee S., Van Duuren B. L. Covalent binding of the carcinogen trichloroethylene to hepatic microsomal proteins and to exogenous DNA in vitro. Cancer Res. 1978 Mar;38(3):776–780. [PubMed] [Google Scholar]
- Banerjee S., Van Duuren B. L., Kline S. A. Interaction of potential metabolites of the carcinogen ethylene dibromide with protein and DNA in vitro. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1214–1220. doi: 10.1016/0006-291x(79)91166-5. [DOI] [PubMed] [Google Scholar]
- Bannon P., Verly W. Alkylation of phosphates and stability of phosphate triesters in DNA. Eur J Biochem. 1972 Nov 21;31(1):103–111. doi: 10.1111/j.1432-1033.1972.tb02506.x. [DOI] [PubMed] [Google Scholar]
- Bhattacharya R. K., Firozi P. F., Aboobaker V. S. Factors modulating the formation of DNA adduct by aflatoxin B1 in vitro. Carcinogenesis. 1984 Oct;5(10):1359–1362. doi: 10.1093/carcin/5.10.1359. [DOI] [PubMed] [Google Scholar]
- Bigger C. A., Tomaszewski J. E., Andrews A. W., Dipple A. Evaluation of metabolic activation of 7,12-dimethylbenz(a)anthracene in vitro by aroclor 1254-induced rat liver S-9 fraction. Cancer Res. 1980 Mar;40(3):655–661. [PubMed] [Google Scholar]
- Bigger C. A., Tomaszewski J. E., Dipple A., Lake R. S. Limitations of metabolic activation systems used with in vitro tests for carcinogens. Science. 1980 Jul 25;209(4455):503–505. doi: 10.1126/science.6771871. [DOI] [PubMed] [Google Scholar]
- Blackburn G. M., Thompson M. H., King H. W. Binding of diethylstilboestrol to deoxyribonucleic acid by rat liver microsomal fractions in vitro and in mouse foetal cells in culture. Biochem J. 1976 Sep 15;158(3):643–646. doi: 10.1042/bj1580643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bolognesi C., Taningher M., Parodi S., Santi L. Quantitative predictivity of carcinogenicity of the autoradiographic repair test (primary hepatocyte cultures) for a group of 80 chemicals belonging to different chemical classes. Environ Health Perspect. 1986 Dec;70:247–253. doi: 10.1289/ehp.8670247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boux L. J., Holder G. M. The activation and DNA binding of 7-methylbenz[c]-acridine catalysed by mouse liver microsomes. Cancer Lett. 1985 Jan;25(3):333–342. doi: 10.1016/s0304-3835(15)30013-6. [DOI] [PubMed] [Google Scholar]
- Bratcher S. C., Sikka H. C. Binding of 3,3'-dichlorobenzidine to DNA and polyribonucleotides in vitro. Chem Biol Interact. 1982 Feb;38(3):369–375. doi: 10.1016/0009-2797(82)90066-7. [DOI] [PubMed] [Google Scholar]
- Chou M. W., Yang S. K. Identification of four trans-3,4-dihydrodiol metabolites of 7,12-dimethylbenz[a]anthracene and their in vitro DNA-binding activities upon further metabolism. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5466–5470. doi: 10.1073/pnas.75.11.5466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colacci A., Arfellini G., Mazzullo M., Prodi G., Grilli S. Genotoxicity of 1,1-dichloroethane. Res Commun Chem Pathol Pharmacol. 1985 Aug;49(2):243–254. [PubMed] [Google Scholar]
- Colacci A., Arfellini G., Mazzullo M., Prodi G., Grilli S. The covalent binding of bromobenzene with nucleic acids. Toxicol Pathol. 1985;13(4):276–282. doi: 10.1177/019262338501300404. [DOI] [PubMed] [Google Scholar]
- Colacci A., Grilli S., Lattanzi G., Prodi G., Paola Turina M., Cantelli Forti G., Mazzullo M. The covalent binding of 1,1,2,2-tetrachloroethane to macromolecules of rat and mouse organs. Teratog Carcinog Mutagen. 1987;7(5):465–474. doi: 10.1002/tcm.1770070504. [DOI] [PubMed] [Google Scholar]
- Colacci A., Mazzullo M., Arfellini G., Prodi G., Grilli S. In vitro microsome- and cytosol-mediated binding of 1,2-dichloroethane and 1,2-dibromoethane with DNA. Cell Biol Toxicol. 1985 Jan;1(2):45–55. doi: 10.1007/BF00717790. [DOI] [PubMed] [Google Scholar]
- Coombs M. M., Bhatt T. S., Vose C. W. The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor. Cancer Res. 1975 Feb;35(2):305–309. [PubMed] [Google Scholar]
- Eastman A., Bresnick E. Metabolism and DNA binding of 3-methylcholanthrene. Cancer Res. 1979 Nov;39(11):4316–4321. [PubMed] [Google Scholar]
- Essigmann J. M., Croy R. G., Nadzan A. M., Busby W. F., Jr, Reinhold V. N., Büchi G., Wogan G. N. Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro. Proc Natl Acad Sci U S A. 1977 May;74(5):1870–1874. doi: 10.1073/pnas.74.5.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garner R. C., Martin C. N., Smith J. R., Coles B. F., Tolson M. R. Comparison of aflatoxin B1 and aflatoxin G1 binding to cellular macromolecules in vitro, in vivo and after peracid oxidation; characterisation of the major nucleic acid adducts. Chem Biol Interact. 1979 Jun;26(1):57–73. doi: 10.1016/0009-2797(79)90093-0. [DOI] [PubMed] [Google Scholar]
- Gold L. S., Sawyer C. B., Magaw R., Backman G. M., de Veciana M., Levinson R., Hooper N. K., Havender W. R., Bernstein L., Peto R. A carcinogenic potency database of the standardized results of animal bioassays. Environ Health Perspect. 1984 Dec;58:9–319. doi: 10.1289/ehp.84589. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grilli S., Arfellini G., Colacci A., Mazzullo M., Prodi G. In vivo and in vitro covalent binding of chlorobenzene to nucleic acids. Jpn J Cancer Res. 1985 Aug;76(8):745–751. [PubMed] [Google Scholar]
- Grilli S., Ferreri A. M., Rocchi P., Prodi G. In vivo and in vitro binding of ethionine with nucleic acids. Gan. 1974 Dec;65(6):507–511. [PubMed] [Google Scholar]
- Grilli S., Rocchi P., Prodi G. Non-enzymatic and microsome-dependent binding of poly-cyclic hydrocarbons to DNA and polynucleotides. Chem Biol Interact. 1975 Nov;11(5):351–363. doi: 10.1016/0009-2797(75)90004-6. [DOI] [PubMed] [Google Scholar]
- Guengerich F. P. Similarity of nuclear and microsomal cytochromes P-450 in the in vitro activation of aflatoxin B1. Biochem Pharmacol. 1979 Oct 1;28(19):2883–2890. doi: 10.1016/0006-2952(79)90583-5. [DOI] [PubMed] [Google Scholar]
- Gurtoo H. L., Dave C. V. In vitro metabolic conversion of aflatoxins and benzo(alpha)pyrene to nucleic acid-binding metabolites. Cancer Res. 1975 Feb;35(2):382–389. [PubMed] [Google Scholar]
- Hashimoto Y., Takeda K., Shudo K., Okamoto T., Sugimura T., Kosuge T. Rat liver microsome-mediated binding to DNA of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a potent mutagen isolated from tryptophan pyrolysate. Chem Biol Interact. 1978 Oct;23(1):137–140. doi: 10.1016/0009-2797(78)90047-9. [DOI] [PubMed] [Google Scholar]
- Hayatsu H., Ukita T. The mofidication of nucleosides and nucleotides. IV. The reaction of semicarbazide with nucleic acids. Biochim Biophys Acta. 1966 Sep;123(3):458–470. [PubMed] [Google Scholar]
- Hemminki K. Binding of metabolites of cyclophosphamide to DNA in a rat liver microsomal system and in vivo in mice. Cancer Res. 1985 Sep;45(9):4237–4243. [PubMed] [Google Scholar]
- Hesse S., Jernström B., Martinez M., Moldéus P., Christodoulides L., Ketterer B. Inactivation of DNA-binding metabolites of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by glutathione and glutathione S-transferases. Carcinogenesis. 1982;3(7):757–761. doi: 10.1093/carcin/3.7.757. [DOI] [PubMed] [Google Scholar]
- Inskeep P. B., Guengerich F. P. Glutathione-mediated binding of dibromoalkanes to DNA: specificity of rat glutathione-S-transferases and dibromoalkane structure. Carcinogenesis. 1984 Jun;5(6):805–808. doi: 10.1093/carcin/5.6.805. [DOI] [PubMed] [Google Scholar]
- Ioannou Y. M., Wilson A. G., Anderson M. W. Effect of butylated hydroxyanisole on the metabolism of benzo[a]-pyrene and the binding of metabolites to DNA, in vitro and in vivo, in the forestomach, lung, and liver of mice. Carcinogenesis. 1982;3(7):739–745. doi: 10.1093/carcin/3.7.739. [DOI] [PubMed] [Google Scholar]
- Iverson F., Ryan J. J., Lizotte R., Hierlihy S. L. In vivo and in vitro binding of alpha- and gamma-hexachlorocyclohexane to mouse liver macromolecules. Toxicol Lett. 1984 Mar;20(3):331–335. doi: 10.1016/0378-4274(84)90168-1. [DOI] [PubMed] [Google Scholar]
- Jaggi W., Lutz W. K., Schlatter C. Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems. Experientia. 1979 May 15;35(5):631–632. doi: 10.1007/BF01960365. [DOI] [PubMed] [Google Scholar]
- Jernström B., Vadi H., Orrenius S. Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA. Cancer Res. 1976 Nov;36(11 Pt 1):4107–4113. [PMC free article] [PubMed] [Google Scholar]
- Kerklaan P. R., Bouter S., van Elburg P. A., Mohn G. R. Evaluation of the DNA-repair host-mediated assay. I. Induction of repairable DNA damage in E. coli cells recovered from liver, spleen, lungs, kidneys, and the blood stream of mice treated with methylating carcinogens. Mutat Res. 1985 Jan-Feb;148(1-2):1–12. doi: 10.1016/0027-5107(85)90202-7. [DOI] [PubMed] [Google Scholar]
- LAWLEY P. D., BROOKES P. FURTHER STUDIES ON THE ALKYLATION OF NUCLEIC ACIDS AND THEIR CONSTITUENT NUCLEOTIDES. Biochem J. 1963 Oct;89:127–138. doi: 10.1042/bj0890127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai D. Y., Arcos J. C., Argus M. F. Factors influencing the microsome- and mitochondria-catalyzed in vitro binding of diethylnitrosamine and N-nitrosopiperidine to deoxyribonucleic acid. Biochem Pharmacol. 1979 Dec 15;28(24):3545–3550. doi: 10.1016/0006-2952(79)90399-x. [DOI] [PubMed] [Google Scholar]
- Lai D. Y., Myers S. C., Woo Y. T., Greene E. J., Friedman M. A., Argus M. F., Arcos J. C. Role of dimethylnitrosamine-demethylase in the metabolic activation of dimethylinitrosamine. Chem Biol Interact. 1979;28(1):107–126. doi: 10.1016/0009-2797(79)90118-2. [DOI] [PubMed] [Google Scholar]
- Lattanzi G., Colacci A., Grilli S., Mazzullo M., Prodi G., Taningher M., Turina M. P. Binding of hexachloroethane to biological macromolecules from rat and mouse organs. J Toxicol Environ Health. 1988;24(3):403–411. doi: 10.1080/15287398809531170. [DOI] [PubMed] [Google Scholar]
- Lawley P. D., Orr D. J., Shah S. A., Farmer P. B., Jarman M. Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methylthymidine. Biochem J. 1973 Sep;135(1):193–201. doi: 10.1042/bj1350193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lotlikar P. D., Clearfield M. S., Jhee E. C. Effect of butylated hydroxyanisole on in vivo and in vitro hepatic aflatoxin B1-DNA binding in rats. Cancer Lett. 1984 Oct;24(3):241–250. doi: 10.1016/0304-3835(84)90019-3. [DOI] [PubMed] [Google Scholar]
- Lubet R. A., Capdevila J., Prough R. A. The metabolic activation of benzo(a)pyrene and 9-hydroxybenzo(a)pyrene by liver microsomal fractions. Int J Cancer. 1979 Mar 15;23(3):353–357. doi: 10.1002/ijc.2910230313. [DOI] [PubMed] [Google Scholar]
- Lutz W. K. In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis. Mutat Res. 1979 Dec;65(4):289–356. doi: 10.1016/0165-1110(79)90006-x. [DOI] [PubMed] [Google Scholar]
- Lutz W. K. Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens. J Cancer Res Clin Oncol. 1986;112(2):85–91. doi: 10.1007/BF00404387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mazzullo M., Colacci A., Grilli S., Prodi G., Arfellini G. 1,1,2-Trichloroethane: evidence of genotoxicity from short-term tests. Jpn J Cancer Res. 1986 Jun;77(6):532–539. [PubMed] [Google Scholar]
- Mazzullo M., Colacci A., Grilli S., Prodi G., Arfellini G. In vivo and in vitro binding of epichlorohydrin to nucleic acids. Cancer Lett. 1984 May;23(1):81–90. doi: 10.1016/0304-3835(84)90065-x. [DOI] [PubMed] [Google Scholar]
- Mazzullo M., Grilli S., Lattanzi G., Prodi G., Turina M. P., Colacci A. Evidence of DNA binding activity of perchloroethylene. Res Commun Chem Pathol Pharmacol. 1987 Nov;58(2):215–235. [PubMed] [Google Scholar]
- McCann J., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci U S A. 1976 Mar;73(3):950–954. doi: 10.1073/pnas.73.3.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller R. E., Guengerich F. P. Metabolism of trichloroethylene in isolated hepatocytes, microsomes, and reconstituted enzyme systems containing cytochrome P-450. Cancer Res. 1983 Mar;43(3):1145–1152. [PubMed] [Google Scholar]
- Mirsalis J. C., Butterworth B. E. Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: an in vivo- in vitro assay for potential carcinogens and mutagens. Carcinogenesis. 1980 Jul;1(7):621–625. doi: 10.1093/carcin/1.7.621. [DOI] [PubMed] [Google Scholar]
- Morimoto K., Tanaka A., Yamaha T. Comparative binding studies on 1,1'-ethylene-bis(1-nitrosourea) and some 1-alkyl-1-nitrosoureas with nucleic acids and proteins in vitro. Gan. 1979 Oct;70(5):693–698. [PubMed] [Google Scholar]
- Nemoto N., Kusumi S., Takayama S., Nagao M., Sugimura T. Metabolic activation of 3-amino-5H-pyrido[4,3-b]indole, a highly mutagenic principle in tryptophan pyrolysate, by rat liver enzymes. Chem Biol Interact. 1979 Oct;27(2-3):191–198. doi: 10.1016/0009-2797(79)90125-x. [DOI] [PubMed] [Google Scholar]
- Nery R., Nice E. The metabolism and binding of ( 14 C)mycophenolic acid in the rat. J Pharm Pharmacol. 1971 Nov;23(11):842–847. doi: 10.1111/j.2042-7158.1971.tb10201.x. [DOI] [PubMed] [Google Scholar]
- Palajda M., Rosenkranz H. S. Assembly and preliminary analysis of a genotoxicity data base for predicting carcinogens. Mutat Res. 1985 May;153(3):79–134. doi: 10.1016/0165-1110(85)90010-7. [DOI] [PubMed] [Google Scholar]
- Parodi S., Taningher M., Russo P., Pala M., Vecchio D., Fassina G., Santi L. Quantitative predictivity of the transformation in vitro assay compared with the Ames test. J Toxicol Environ Health. 1983 Oct-Dec;12(4-6):483–510. doi: 10.1080/15287398309530444. [DOI] [PubMed] [Google Scholar]
- Parodi S., Taningher M., Santi L. Induction of preneoplastic nodules: quantitative predictivity of carcinogenicity. Anticancer Res. 1983 Nov-Dec;3(6):393–399. [PubMed] [Google Scholar]
- Parodi S., Taningher M., Santi L. Utilization of the quantitative component of positive and negative results of short-term tests. Mutat Res. 1988 May-Aug;205(1-4):283–294. doi: 10.1016/0165-1218(88)90023-7. [DOI] [PubMed] [Google Scholar]
- Prodi G., Grilli S., Mazzullo M., Colacci A., Arfellini G. Comparison between photo-induction and microsomal activation of polycyclic hydrocarbons with different oncogenic potency. Toxicol Pathol. 1984;12(2):185–188. doi: 10.1177/019262338401200212. [DOI] [PubMed] [Google Scholar]
- Raj H. G., Clearfield M. S., Lotlikar P. D. Comparative kinetic studies on aflatoxin B1-DNA binding and aflatoxin B1-glutathione conjugation with rat and hamster livers in vitro. Carcinogenesis. 1984 Jul;5(7):879–884. doi: 10.1093/carcin/5.7.879. [DOI] [PubMed] [Google Scholar]
- Ramel C. Short-term testing--are we looking at wrong endpoints? Mutat Res. 1988 May-Aug;205(1-4):13–24. doi: 10.1016/0165-1218(88)90004-3. [DOI] [PubMed] [Google Scholar]
- Rocchi P., Prodi G., Grilli S., Ferreri A. M. In vivo and in vitro binding of carbon tetrachloride with nucleic acids and proteins in rat and mouse liver. Int J Cancer. 1973 Mar 15;11(2):419–425. doi: 10.1002/ijc.2910110219. [DOI] [PubMed] [Google Scholar]
- Sipes I. G., Slocumb M. L., Holtzman G. Stimulation of microsomal dimethylnitrosamine-N-demethylase by pretreatment of mice with acetone. Chem Biol Interact. 1978 Jun;21(2-3):155–166. doi: 10.1016/0009-2797(78)90016-9. [DOI] [PubMed] [Google Scholar]
- Strategies for the deployment of batteries of short-term tests. Mutat Res. 1988 May-Aug;205(1-4):1–423. [PubMed] [Google Scholar]
- Sun L., Singer B. The specificity of different classes of ethylating agents toward various sites of HeLa cell DNA in vitro and in vivo. Biochemistry. 1975 Apr 22;14(8):1795–1802. doi: 10.1021/bi00679a036. [DOI] [PubMed] [Google Scholar]
- Swenson D. H., Lawley P. D. Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine. Biochem J. 1978 Jun 1;171(3):575–587. doi: 10.1042/bj1710575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada M., Takahashi K., Kawazoe Y., Ito N. Binding of quinoline to nucleic acid in a subcellular microsomal system. Chem Biol Interact. 1980 Mar;29(3):257–266. doi: 10.1016/0009-2797(80)90145-3. [DOI] [PubMed] [Google Scholar]
- Tennant R. W., Margolin B. H., Shelby M. D., Zeiger E., Haseman J. K., Spalding J., Caspary W., Resnick M., Stasiewicz S., Anderson B. Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science. 1987 May 22;236(4804):933–941. doi: 10.1126/science.3554512. [DOI] [PubMed] [Google Scholar]
- Turina M. P., Colacci A., Grilli S., Mazzullo M., Prodi G., Lattanzi G. Short-term tests of genotoxicity for 1,1,1-trichloroethane. Res Commun Chem Pathol Pharmacol. 1986 Jun;52(3):305–320. [PubMed] [Google Scholar]
- Williams G. M., Laspia M. F. The detection of various nitrosamines in the hepatocyte primary culture/DNA repair test. Cancer Lett. 1979 Apr;6(4-5):199–206. doi: 10.1016/s0304-3835(79)80034-8. [DOI] [PubMed] [Google Scholar]
