Index Accelerators of nitrosation, 4 y-Aminobutyrate, 173 Activated N-nitrosamines, 73 E-Aminocaproic acid, 172 Agricultural chemicals, 3, 6 Aminopyrine, 6 Aldehydes, 4 Ampicillin, 97 Aliphatic nitrosamines, 203 Ampicillin resistance, 47 Alkanolamines, 4 Analgesic, 5 Alkanesulfonates, 131 Arginine, 6 Alkonium ion, 85, 86 Arylating agent, 86 Alkylated nucleic acids, 201 Aryl groups, 249 Alkylation of DNA, 61, 189 ArK-locus, 236 Alkylating agent, 2, 60, 113, 114,201 Ascorbic acid, 4 Alkylating agent, formation of a reactive, 39 Asymmetrical oxygenated nitrosamines, 210 Alk"yldiazonium ions, 61, 84 06-Alkylguanine, 61, 113,202 06-Alkylguanine, repair activity, 63 Bacon, ni trosamines in, 112 7-Alkylguanine, 71,202 Bacterial mutagenesis tests, 5 Alkyliodides and bromides, 61 Bacterial reduction, 5 Alkylnitrites, 3 Bacteriophage induction assay, 92 Alkylsulfonates, 61,131 Bacteriophage lambda, 91 Alkylureas, 6 Beer, nitrosamines in, 3 Allantoin,6 Benzidine, 163 a-Acetoxy nitrosamines, 169 Benzopyrene, 65 a-I-Antitrypsin, 159 Beta carbon, in nitrosomethylethylamine, 206 Alpha carbon, susceptibility to activation, 219 Betel nuts, 223 Alpha-hydroxylation, 167, 172, 184 5-Bromo-2' -deoxyutidine, 135 Alpha-hydroxynitrosamines, 73, 167 1, 4-Butanediol, 168, 170, 173, 175, 179 Alpha oxidation, 180,214,219,224 inhibition of, 38 Alpha tocopherol, 4 Canavanine resistance, 236 Amine Carbamate insecticides, 100 secondary, 1, 5, 6 Carbonyl compounds, 4 tertiary, 3, 5 Carcinogenic damage, 234 265 266 Index Carcinogenic potency, 123 Dinitroso-2, 6-dimethylpiperazine, 19, 135, 137, Carcinogenic mechanisms, 183 138,217,218 Carcinogenesis, two stage, 199 Dinitrosohomopiperazine, 19, 133,217,258 Carcinogenesis, and structural symmetry, 55 Dinitroso-2-methylpiperazine, 19, 137, 138,217 Carcinogenic risk, 5,6,8 Dinitrosopiperazine, 19,38,49,137,138,217, Carbonyl,6 218,258 Carbonium ion, 168 Diphenhydramine, 6 primary, 86 Dipyrone,6 secondary, 86 Disulfiram, 6 Carboxynitrosopiperidines, 137 DNA Cellular macromolecules, 2, 207 alkylation of, 47, 250, 257 Cheese, 5 binding to protein, 162 Chinese hamster cells, (V79), 120,236 damaging agent, 97 Chinese hamster ovary cell~, 130, 236 repair, 233 Chloral,4 Dose-response curve, 34 Chlordiazepoxide, 6 Dried milk, 4 Chlorpheniramine,6 Drosophila melaIZO"aJter, 236 Chlorpromazine, 6 Drosophila X-linked recessive lethal system, Chromatid breaks, 233 130,236 Chromosomal abberations, 233, 236 Drugs, 3,6 Chromosomal breaks, 236 Cigarette smoke, 212 Clofibrate, 252 Environmental mixtures and effluents, 234 Cosmetic preparations, 4 Epoxide formation, 39,223 Croton oil, 199 Esophageal tumors, 251 Cured meat and fish, 5 Esophagus, methylation in, 203 Cyclic nitrosamines, 16, 38 Ethers, 208 Cyclophosphamide, 136 Ethoxylating agent, 203 Cytochrome-linked mixed function oxidases, 45 Ethylating agents, 114 Cytosolic fraction, 155, 157, 162 Ethylation of DNA, 40 Ethyldiazonium ions, 84 O"-Ethylguanine, 82, 112, 114 Ethylmethanesulfonate, 133 Excision repair deficient mutants, 236 Dealkylation, oxidative, 45 Excision repair system, 47, 48 Deuterium substitution, 206, 211 Dialkylnitrosamines, 102, 168 Dialkylsulfates, 61 Fenuron,6 Diazohydroxide, 168 Filamentation,91 Diazonium ions, 85, 86, 169 Flue gases, 3 Diethanolamine,4 Fluorine, substitution in nitrosamines, 207 Diethylamine, 2 Food preservatives, 129 Dimethylamine, 2, 4, 5, 172 Formaldehyde, 4, 152 Dimethyldodecylamine,6 Dimethyldodecylamine-N-oxide,6 Dimethylnitrosamine, binding to protein, 162 ,l3-Galactosidase, 92, 97 Dimethylnitrosamine de methylase 1,62,65,67, "allocus,.263 149, 152, 155, 157, 160, 161, 162, 163 Gene mutations, 233, 235 Dimethylnitrosamine demethylase II, 152 Genetic toxicants, 235 Dimethylsulfoxide, 150, 159, 163 Genotoxic/ genotoxicity, 203 Dinitroso-2, 5-dimethylpiperazine, 19, 38, 217 Genotoxicology of nitrosamine, 235 Index 267 Genotoxic properties, 233, 235 Lipophobicity, 53 Glutathione, 4 Lipopolysaccharide barrier, 47 Guanine 06-methyltransferase, 113 Liposolubility, 250 Guvacine, 223 Liquid preincubation assay, 13 Liquid suspension assay, 13 Liver necrosis, 1 Haloethanes, 131 Liver parenchymal cells, 251 Hamster liver, S9, 34, 38,96, 163, 254 Lucanthone, 6 Hemangioendothelial sarcomas, 251 Lymphoma of the thymus, 218 Hepatocellular carcinomas, 172 Hepatocytes, 120 Hepatotoxins, 251 Heterocyclic nitrosamines, 131, 167 Mammalian cell systems, 236 1, 6-Hexanediol, 173 Mammalian enzymes, 234 HGPRT, Jee Hypoxanthine-guanine Mammalian stomach, 2 phospho ribosyl transferase Meat-curing mixtures, 129 Human leukocyte culture system, 130, 137 Metabolic activation, 234 Hydrochlorothiazide, 6 Metabolism of N-nitrosamines, 235 Hydrophilic, 211 Metal ions, 4 4-Hydroxybutanal, 175, 179 Methapyrilene, 6, 252 y-Hydroxybutyrate, 168, 170, 172, 173, 175, 179 Methomyl, 249 2-Hydroxyethyl species, 256 3-Methyladenine glycosylase, 113 a-Hydroxylation, 167, 172, 184 Methylating agem, 206, 256, 258 6- H ydroxy-n-hexanal, 180 3-Methylcholanthrene,65 a-Hydroxynitrosamine, 73, 167 Methyldiazonium ion, 84 a-Hydroxnitrosopyrrolidine, see Methylmethanesulfonate,64 Nitroso-2-hydroxypyrrolidine Methylphenidate, 221 ,B-Hydroxynitrosopyrrolidine, Jee 7-Methylguanine, 70,71,78,79 Nitroso-3-hydroxypyrrolidine 06-Methylguanine, 70, 71, 78, 79, 80 2-Hydroxytetrahydrofuran, 168, 169, 171, 172, Methylguanidine,6 173,175,179,184 Methyl groups, oxidizable, 206 Hypoxanthine-guanine phosphoribosyl Methyl substitution, 38 transferase (HGPRT) locus, 130 Microsomal fraction, 155, 157, 162 Microsomes metabolism by, 161 Inhibition of nitrosation, 4 supernatant, 173, 178, 184 Initiators, 199 Milk,129 Insecticides, nitroso-derivatives of, 6, 106 Mitosis, 225 Molecular configuration and conformation, 212 Monomethylnitrosamine,61 Monuron,6 Kinetic assay of induction, 97 Morpholine, 4, 6,214 Kupffer cells, 172 analogs, 109 derivatives, 103 Mouse liver, S9, 150 Lambda repressor, 91, 92,113 Mouse skin, 189 Lambda lysogen,92 Mouse skin assay, 249 Leukemia of the thymus, 218 Multiplex CHO system, 131 Leukocytes, human, 236 Mutagenesis Lex A mutation, 94 and aliphatic nitrosamines, 54,73 Lipophilic, 211 and chemical ring size, 49 268 Index Mutagenesis, (collta) N-Nitroso-, (collt'd) and chemical ring substitution, 51 benzylurea, 41, 201, 250 DNA repair in, 48 bis-(2-chloroethyl)amine, 54, 208, 209 and halogen substitution, 52 bis-(2-chloropropyl)amine, 54, 209 nitrosamines as model compounds in, 56 bis-(2,2-diethoxyethyl)amine,209 NMU-induced,81 bis-(2-ethoxyethyl)amine,208 and structural symmetry, 55 bis-(2-cyanoethyl)amine, 85, 208 Mutagenic intermediates, 120 bis-(2-cyanomethyl)amine, 208, 209 Mutagenicity, chemical structure and, 34, 38,48 bis-(2-hydroxypropyl)amine, 4, 24,40, 54, Mutagenic potency, 74, 122 163,207,209,210,254 and chemical structute, 13 bis-(2-methoxyethyl)amine, 54, 208 Mutants, canavanine-resistant, 46 bis-(2-oxopropyl)amine, 24, 40, 210, 254 Mutations, reversion and forward, 236 bis-(2-trifluoroethyl)amine, 209 4-t-butylpiperidine, 19, 39, 83, 86, 219, 221 n_butylurea,201 Nad locus, 236 buxten, 104 Neurospora conidia, 46 carbaryl, 6, 104, 199 Nitrilotriacetic acid, 6 carbofuran, 104 Nitrite, 4, 5 3-chloropiperidine, 52, 224 Nitrite, fish and meat cured with, 5 4-chloropiperidine, 52,137,224 Nitrogen oxides, 3 cimetidine, 28, 249, 257 Nitrosamides, 28,60 4-cyclohexylpiperidine, 19,39,105,109,222 Nirrosamines cyclohexylurea, 20 I activated, 184 diallylamine, 24, 40, 54,121,209,211,239, acyclic, 24,40, 239 254 in air, 4 dibenzylamine, 39, 207 aromatic, 24 3, 4-dibromopiperidine, 52, 105,224 asymmetric, oxygenated, 210 3, 4-dibromopyrrolidine, 52, 221 cyclic, 48, 49, 102, 168, 172, 180, 240, 245 di-sec-butylamine,86 cyclic alkylated, 52 di-n-butylamine, 24, 40, 102, 163, 205, 258 dialkyl,48, 168 3, 4-dichloropiperidine, 52, 105, 137,224 mutagenic activity of, 184 3, 4-dichloropyrrolidine, 221 nonmutagenic,253 diethanolamine, 4, 24, 40, 41, 54, 86, 203,207, a-substituted, 86 208,209,210,252,253,256 /3-substituted carcinogenic, 85 diethylamine, 2, 24, 40, 63, 81, 85, 94,101, N-Nitrosamines, 63, 64,120,131,172,239 108, 121, 133, 163,201,203,204,205,207, Nitrosating agents, 2 251,258 N-Nitroso- 2, 3-dihydroxypropylallylamine, 28, 41 acetoxydibenzylamine, 24, 39, 203 dihydroxypropylethanolamine, 28, 41, 211 acetoxydimethylamine, 203 dihydroxypropyl-2-oxopropylamine, 28, 211 4-acetyl-3, 5-dimethylpiperazine, 19, 38,219 di-isobutylamine, 24,40, 258 aldicarb, 104 di-isopropanolamine, see allylethanolamine, 28, 211 bis (2 -hydroxypropy I) amine allylhydroxypropylamine, 28, 211 di-isopropylamine, 4, 86, 203 allylurea, 107,201,257 dimethylamine, 1,4,24,40,45,46,61,63,74, n-amylurea,201 85,94,101,108,121,132,133,149,152, anabasine, 220 155,161,189,201,204,205,251,256 azetidine, 16,38,49, 103,212 2, 6-dimethylmorpholine, 19, 215, 218, 248, baygon,106 258 4-benzoyl-3, 5-dimethylpiperazine, 19, 38, 2, 6-dimethylmorpholine-cis and trans, 103, 219,254 109,215 Index 269 N-Nitroso-, (com'ti) N-Nitroso-, (col1t'd) 2, 4-dimethyl-l, 3-oxazolidine, 16 iminodipropionitrile, see 4, 4-dimethyl-l, 3-oxazolidine, 16 bis-(2-cyanoethyl)amine 3, 5-dimethylpiperazine, 19,218,219 isobutylurea, 41, 250 2, 6-dimethylpiperidine, 52, 86, 137,221 isonipecotic acid, 53, 223 3, 5-dimethypiperidine, 19,39,51 2-isopropyl-4, 4-dimethyl-l, 3-oxazolidine, 16 3. 5-dimethylpiperidine-cis and trans, 19 isopropylurea,201 2, 5-dimethylpyrrolidine, 133,219 landrin, 104 di-n-octylamine, 24, 40, 54, 205 methomyl, 104 diphenylamine, 3, 24, 39, 203, 255 methylacetonitrile, 209 di-n-propylamine, 24, 40,86,201,208,209, methylallylamine,