Table 2.
Open in new tab

The nitrosamines DBPs mediate metabolic disorders in different tumors

Tumor typeStudy typeSubjectsThe levels of nitrosamines DBPsMetabolitesMetabolic pathways
Colorectal cancer (Luo et al., 2022)Case-control studyHuman (plasma samples)

  • NDMAD (56.5% vs 97.1%)

  • NPYR (17.4% vs 91.2%)

Downregulation

  • Pyruvate; triphosphoglyceric acid

  • γ-aminobutyric acid; l-glutamic acid

  • Hypoxanthine; acetylcarnitine

  • Lysophosphatidic acid (20:4, 20:5)

  • Hemolytic phosphatidylserine (20:4, 22:6)

  • Hypoxanthine and xanthine metabolic pathways

  • Taurine and hypotaurine metabolic pathways

  • Arginine and proline metabolic pathways

  • The 2-oxocarboxylic acidmetabolic pathway

  • Alanine, aspartic acid, and glutamic acid metabolic pathways

  • Glyoxylic acid and dicarboxylic acid metabolic pathways

Upregulation

  • Itric acid; xanthuric acid

  • Lyso-phosphatidylcholine 16:1

  • 7-Methylguanosine; adenosine 5′-monophosphate

Esophageal squamous cell carcinoma (Zhao, 2021)Case-control studyHuman (plasma samples)

  • NDMA (0.245 vs 0.406 ng/ml)

  • NDBA (ND vs 0.094 ng/ml)

  • NDphA (ND vs 0.058 ng/ml)

  • NPyr (0.144 vs 0.30 ng/ml)

  • NDPA (ND∼0.064 vs ND∼0.182 ng/ml)

Downregulation

  • Sphingosine; tryptophan

  • Indole-3-acetic acid; serotonin

  • Alanine, aspartate, and glutamate metabolism

  • Phenylalanine metabolism

  • Arginine biosynthesis

  • d-Glutamine and d-glutamate metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

UpregulationDihydrosphingosine; sphingosine-1-phosphate; dihydrosphingosine-1-phosphate; quinolinic acid
Esophageal squamous cell carcinoma (Zhang et al., 2022a)Experimental StudyMalignant transformation Het-1a cellsMNNG (2 μmol/l)DownregulationCosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Linoleic acid metabolism

  • Arachidonic acid metabolism

  • Alpha-linolenic acid metabolism

  • Glycerophospholipid metabolism

Upregulation

  • Linoleate; hexadecanoic acid

  • Octadecanoic acid; arachidonate

Esophageal squamous cell carcinoma (Zhang et al., 2022c)Experimental StudyMice (serum and urine samples)

  • The nitrosamines mixture

  • Low dose group (7.5 ng/kg)

  • Medium dose group (3 μg/kg)

  • High dose group (1.2 mg/kg)

Downregulation

  • Palmitic acid; linoleic acid

  • y-Linoleic acid; arachidonic acid

  • Docosahexaenoic acid

  • Eicosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Alpha-linolenic acid metabolism

  • Pentose phosphate metabolism

  • Glycerophospholipid metabolism

  • β-Alanine metabolism

  • Glutathione metabolism

  • Sphingolipid metabolism

UpregulationPalmitoylcarntine
Esophageal squamous cell carcinoma (Zhao et al., 2022a)Experimental StudyMice (serum samples)NMBA (0.4 mg/kg)Downregulation

  • Heptanoic acids; palmitic acid

  • Stearic acid; oleic acid

  • l-Palmitoylcarnitine; acetylcarnitine

  • Alanine, aspartate, and glutamate metabolism

  • Arginine and proline metabolism

  • Arginine biosynthesis

  • Nicotinate and nicotinamide metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

Upregulation

  • Glycocholic acid; taurocholic acid

  • Sphingosine-1-phosphate

Hepatocellular carcinoma (Ding et al., 2020)Experimental StudyMice (liver tissues samples)DEN (100 mg/l DEN in drinking water)UpregulationProlineProline metabolic pathway
Bladder cancer (Afify et al., 2021)Experimental StudyMice (bladders tissues samples)BBN (0.05% in drinking water)Upregulation

  • Glycerphosphoethanolamine

  • Glycerphosphocholine

  • Glycerophosphoserine

  • Glycerophosphoglycerol

  • Lysophospholipids

  • TCA cycle

  • Fatty acid, dicarboxylate

  • Tryptophan metabolism

  • Glutamate metabolism

  • Purine metabolism

  • Phospholipid metabolism

Hepatocellular carcinoma (Yang et al., 2018)Experimental StudyMice (serum and urine samples)DEN (50 mg/kg DEN intraperitoneal injection)Downregulation

  • Leucine; isoleucine; valine; lactate

  • 3-Hydroxybutyrate; glutamine; glycine; formate

—
UpregulationAcetate; glutamate; tyrosine
Hepatocellular carcinoma (Wang et al., 2022)Experimental StudyMice (urine samples)DEN (60 mg/l DEN intraperitoneal injection)Upregulation

  • Hippurate; creatinine; putrescine

  • Choline; taurinedimethylglycine

  • Glycine, serine, and threonine metabolism

  • Taurine and hypotaurine metabolism

  • Arginine and proline metabolism

  • Primary bile acid biosynthesis

Hepatocellular carcinoma (Peng et al., 2015)Experimental StudyMice (liver tissues samples)DEN (80 mg/l DEN intraperitoneal injection)Downregulation

  • Lactate; palmitelaidic acid

  • Glycerol 3-phosphate; d-glucose

  • Amino acid metabolism (33.33%)

  • Carbohydrate metabolism (41.33%)

  • Lipids metabolism (21.33%)

  • Nucleotides metabolism (4.00%)

Upregulationl-glutamine; l-aspartate; malate
Hepatocellular carcinoma (Haberl et al., 2021)Experimental StudyMice (liver tissues samples)DEN (25 µg/g DEN intraperitoneal injection)Downregulation

  • Monounsaturated lysophosphatidylethanolamine

  • Monounsaturated phospholipids phosphatidylserine

  • Phosphatidylcholine (PC34:2, PC36:3, PC40:7)

—
Upregulation

  • Triglyceride

  • Cholesterol (16:0, 16:1, 18:1, 18:2, 20:4, 22:6)

  • Ceramide ((d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/23:0, d18:1/24:1)

  • Monounsaturated phosphatidylinositol

—
Hepatocellular carcinoma (Chen et al., 2019)Experimental StudyMice (liver tissues samples)DEN (5 μg/g DEN intraperitoneal injection)Downregulationα-Glucose; β-glucose

  • Lipid metabolism

  • Amino acid metabolism

Upregulation

  • Lactate; creatine; acetate; valine; glutamate; alanine; lysine; histidine

  • Glutamine; glycine; glutathione

Tumor typeStudy typeSubjectsThe levels of nitrosamines DBPsMetabolitesMetabolic pathways
Colorectal cancer (Luo et al., 2022)Case-control studyHuman (plasma samples)

  • NDMAD (56.5% vs 97.1%)

  • NPYR (17.4% vs 91.2%)

Downregulation

  • Pyruvate; triphosphoglyceric acid

  • γ-aminobutyric acid; l-glutamic acid

  • Hypoxanthine; acetylcarnitine

  • Lysophosphatidic acid (20:4, 20:5)

  • Hemolytic phosphatidylserine (20:4, 22:6)

  • Hypoxanthine and xanthine metabolic pathways

  • Taurine and hypotaurine metabolic pathways

  • Arginine and proline metabolic pathways

  • The 2-oxocarboxylic acidmetabolic pathway

  • Alanine, aspartic acid, and glutamic acid metabolic pathways

  • Glyoxylic acid and dicarboxylic acid metabolic pathways

Upregulation

  • Itric acid; xanthuric acid

  • Lyso-phosphatidylcholine 16:1

  • 7-Methylguanosine; adenosine 5′-monophosphate

Esophageal squamous cell carcinoma (Zhao, 2021)Case-control studyHuman (plasma samples)

  • NDMA (0.245 vs 0.406 ng/ml)

  • NDBA (ND vs 0.094 ng/ml)

  • NDphA (ND vs 0.058 ng/ml)

  • NPyr (0.144 vs 0.30 ng/ml)

  • NDPA (ND∼0.064 vs ND∼0.182 ng/ml)

Downregulation

  • Sphingosine; tryptophan

  • Indole-3-acetic acid; serotonin

  • Alanine, aspartate, and glutamate metabolism

  • Phenylalanine metabolism

  • Arginine biosynthesis

  • d-Glutamine and d-glutamate metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

UpregulationDihydrosphingosine; sphingosine-1-phosphate; dihydrosphingosine-1-phosphate; quinolinic acid
Esophageal squamous cell carcinoma (Zhang et al., 2022a)Experimental StudyMalignant transformation Het-1a cellsMNNG (2 μmol/l)DownregulationCosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Linoleic acid metabolism

  • Arachidonic acid metabolism

  • Alpha-linolenic acid metabolism

  • Glycerophospholipid metabolism

Upregulation

  • Linoleate; hexadecanoic acid

  • Octadecanoic acid; arachidonate

Esophageal squamous cell carcinoma (Zhang et al., 2022c)Experimental StudyMice (serum and urine samples)

  • The nitrosamines mixture

  • Low dose group (7.5 ng/kg)

  • Medium dose group (3 μg/kg)

  • High dose group (1.2 mg/kg)

Downregulation

  • Palmitic acid; linoleic acid

  • y-Linoleic acid; arachidonic acid

  • Docosahexaenoic acid

  • Eicosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Alpha-linolenic acid metabolism

  • Pentose phosphate metabolism

  • Glycerophospholipid metabolism

  • β-Alanine metabolism

  • Glutathione metabolism

  • Sphingolipid metabolism

UpregulationPalmitoylcarntine
Esophageal squamous cell carcinoma (Zhao et al., 2022a)Experimental StudyMice (serum samples)NMBA (0.4 mg/kg)Downregulation

  • Heptanoic acids; palmitic acid

  • Stearic acid; oleic acid

  • l-Palmitoylcarnitine; acetylcarnitine

  • Alanine, aspartate, and glutamate metabolism

  • Arginine and proline metabolism

  • Arginine biosynthesis

  • Nicotinate and nicotinamide metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

Upregulation

  • Glycocholic acid; taurocholic acid

  • Sphingosine-1-phosphate

Hepatocellular carcinoma (Ding et al., 2020)Experimental StudyMice (liver tissues samples)DEN (100 mg/l DEN in drinking water)UpregulationProlineProline metabolic pathway
Bladder cancer (Afify et al., 2021)Experimental StudyMice (bladders tissues samples)BBN (0.05% in drinking water)Upregulation

  • Glycerphosphoethanolamine

  • Glycerphosphocholine

  • Glycerophosphoserine

  • Glycerophosphoglycerol

  • Lysophospholipids

  • TCA cycle

  • Fatty acid, dicarboxylate

  • Tryptophan metabolism

  • Glutamate metabolism

  • Purine metabolism

  • Phospholipid metabolism

Hepatocellular carcinoma (Yang et al., 2018)Experimental StudyMice (serum and urine samples)DEN (50 mg/kg DEN intraperitoneal injection)Downregulation

  • Leucine; isoleucine; valine; lactate

  • 3-Hydroxybutyrate; glutamine; glycine; formate

—
UpregulationAcetate; glutamate; tyrosine
Hepatocellular carcinoma (Wang et al., 2022)Experimental StudyMice (urine samples)DEN (60 mg/l DEN intraperitoneal injection)Upregulation

  • Hippurate; creatinine; putrescine

  • Choline; taurinedimethylglycine

  • Glycine, serine, and threonine metabolism

  • Taurine and hypotaurine metabolism

  • Arginine and proline metabolism

  • Primary bile acid biosynthesis

Hepatocellular carcinoma (Peng et al., 2015)Experimental StudyMice (liver tissues samples)DEN (80 mg/l DEN intraperitoneal injection)Downregulation

  • Lactate; palmitelaidic acid

  • Glycerol 3-phosphate; d-glucose

  • Amino acid metabolism (33.33%)

  • Carbohydrate metabolism (41.33%)

  • Lipids metabolism (21.33%)

  • Nucleotides metabolism (4.00%)

Upregulationl-glutamine; l-aspartate; malate
Hepatocellular carcinoma (Haberl et al., 2021)Experimental StudyMice (liver tissues samples)DEN (25 µg/g DEN intraperitoneal injection)Downregulation

  • Monounsaturated lysophosphatidylethanolamine

  • Monounsaturated phospholipids phosphatidylserine

  • Phosphatidylcholine (PC34:2, PC36:3, PC40:7)

—
Upregulation

  • Triglyceride

  • Cholesterol (16:0, 16:1, 18:1, 18:2, 20:4, 22:6)

  • Ceramide ((d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/23:0, d18:1/24:1)

  • Monounsaturated phosphatidylinositol

—
Hepatocellular carcinoma (Chen et al., 2019)Experimental StudyMice (liver tissues samples)DEN (5 μg/g DEN intraperitoneal injection)Downregulationα-Glucose; β-glucose

  • Lipid metabolism

  • Amino acid metabolism

Upregulation

  • Lactate; creatine; acetate; valine; glutamate; alanine; lysine; histidine

  • Glutamine; glycine; glutathione

Table 2.
Open in new tab

The nitrosamines DBPs mediate metabolic disorders in different tumors

Tumor typeStudy typeSubjectsThe levels of nitrosamines DBPsMetabolitesMetabolic pathways
Colorectal cancer (Luo et al., 2022)Case-control studyHuman (plasma samples)

  • NDMAD (56.5% vs 97.1%)

  • NPYR (17.4% vs 91.2%)

Downregulation

  • Pyruvate; triphosphoglyceric acid

  • γ-aminobutyric acid; l-glutamic acid

  • Hypoxanthine; acetylcarnitine

  • Lysophosphatidic acid (20:4, 20:5)

  • Hemolytic phosphatidylserine (20:4, 22:6)

  • Hypoxanthine and xanthine metabolic pathways

  • Taurine and hypotaurine metabolic pathways

  • Arginine and proline metabolic pathways

  • The 2-oxocarboxylic acidmetabolic pathway

  • Alanine, aspartic acid, and glutamic acid metabolic pathways

  • Glyoxylic acid and dicarboxylic acid metabolic pathways

Upregulation

  • Itric acid; xanthuric acid

  • Lyso-phosphatidylcholine 16:1

  • 7-Methylguanosine; adenosine 5′-monophosphate

Esophageal squamous cell carcinoma (Zhao, 2021)Case-control studyHuman (plasma samples)

  • NDMA (0.245 vs 0.406 ng/ml)

  • NDBA (ND vs 0.094 ng/ml)

  • NDphA (ND vs 0.058 ng/ml)

  • NPyr (0.144 vs 0.30 ng/ml)

  • NDPA (ND∼0.064 vs ND∼0.182 ng/ml)

Downregulation

  • Sphingosine; tryptophan

  • Indole-3-acetic acid; serotonin

  • Alanine, aspartate, and glutamate metabolism

  • Phenylalanine metabolism

  • Arginine biosynthesis

  • d-Glutamine and d-glutamate metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

UpregulationDihydrosphingosine; sphingosine-1-phosphate; dihydrosphingosine-1-phosphate; quinolinic acid
Esophageal squamous cell carcinoma (Zhang et al., 2022a)Experimental StudyMalignant transformation Het-1a cellsMNNG (2 μmol/l)DownregulationCosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Linoleic acid metabolism

  • Arachidonic acid metabolism

  • Alpha-linolenic acid metabolism

  • Glycerophospholipid metabolism

Upregulation

  • Linoleate; hexadecanoic acid

  • Octadecanoic acid; arachidonate

Esophageal squamous cell carcinoma (Zhang et al., 2022c)Experimental StudyMice (serum and urine samples)

  • The nitrosamines mixture

  • Low dose group (7.5 ng/kg)

  • Medium dose group (3 μg/kg)

  • High dose group (1.2 mg/kg)

Downregulation

  • Palmitic acid; linoleic acid

  • y-Linoleic acid; arachidonic acid

  • Docosahexaenoic acid

  • Eicosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Alpha-linolenic acid metabolism

  • Pentose phosphate metabolism

  • Glycerophospholipid metabolism

  • β-Alanine metabolism

  • Glutathione metabolism

  • Sphingolipid metabolism

UpregulationPalmitoylcarntine
Esophageal squamous cell carcinoma (Zhao et al., 2022a)Experimental StudyMice (serum samples)NMBA (0.4 mg/kg)Downregulation

  • Heptanoic acids; palmitic acid

  • Stearic acid; oleic acid

  • l-Palmitoylcarnitine; acetylcarnitine

  • Alanine, aspartate, and glutamate metabolism

  • Arginine and proline metabolism

  • Arginine biosynthesis

  • Nicotinate and nicotinamide metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

Upregulation

  • Glycocholic acid; taurocholic acid

  • Sphingosine-1-phosphate

Hepatocellular carcinoma (Ding et al., 2020)Experimental StudyMice (liver tissues samples)DEN (100 mg/l DEN in drinking water)UpregulationProlineProline metabolic pathway
Bladder cancer (Afify et al., 2021)Experimental StudyMice (bladders tissues samples)BBN (0.05% in drinking water)Upregulation

  • Glycerphosphoethanolamine

  • Glycerphosphocholine

  • Glycerophosphoserine

  • Glycerophosphoglycerol

  • Lysophospholipids

  • TCA cycle

  • Fatty acid, dicarboxylate

  • Tryptophan metabolism

  • Glutamate metabolism

  • Purine metabolism

  • Phospholipid metabolism

Hepatocellular carcinoma (Yang et al., 2018)Experimental StudyMice (serum and urine samples)DEN (50 mg/kg DEN intraperitoneal injection)Downregulation

  • Leucine; isoleucine; valine; lactate

  • 3-Hydroxybutyrate; glutamine; glycine; formate

—
UpregulationAcetate; glutamate; tyrosine
Hepatocellular carcinoma (Wang et al., 2022)Experimental StudyMice (urine samples)DEN (60 mg/l DEN intraperitoneal injection)Upregulation

  • Hippurate; creatinine; putrescine

  • Choline; taurinedimethylglycine

  • Glycine, serine, and threonine metabolism

  • Taurine and hypotaurine metabolism

  • Arginine and proline metabolism

  • Primary bile acid biosynthesis

Hepatocellular carcinoma (Peng et al., 2015)Experimental StudyMice (liver tissues samples)DEN (80 mg/l DEN intraperitoneal injection)Downregulation

  • Lactate; palmitelaidic acid

  • Glycerol 3-phosphate; d-glucose

  • Amino acid metabolism (33.33%)

  • Carbohydrate metabolism (41.33%)

  • Lipids metabolism (21.33%)

  • Nucleotides metabolism (4.00%)

Upregulationl-glutamine; l-aspartate; malate
Hepatocellular carcinoma (Haberl et al., 2021)Experimental StudyMice (liver tissues samples)DEN (25 µg/g DEN intraperitoneal injection)Downregulation

  • Monounsaturated lysophosphatidylethanolamine

  • Monounsaturated phospholipids phosphatidylserine

  • Phosphatidylcholine (PC34:2, PC36:3, PC40:7)

—
Upregulation

  • Triglyceride

  • Cholesterol (16:0, 16:1, 18:1, 18:2, 20:4, 22:6)

  • Ceramide ((d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/23:0, d18:1/24:1)

  • Monounsaturated phosphatidylinositol

—
Hepatocellular carcinoma (Chen et al., 2019)Experimental StudyMice (liver tissues samples)DEN (5 μg/g DEN intraperitoneal injection)Downregulationα-Glucose; β-glucose

  • Lipid metabolism

  • Amino acid metabolism

Upregulation

  • Lactate; creatine; acetate; valine; glutamate; alanine; lysine; histidine

  • Glutamine; glycine; glutathione

Tumor typeStudy typeSubjectsThe levels of nitrosamines DBPsMetabolitesMetabolic pathways
Colorectal cancer (Luo et al., 2022)Case-control studyHuman (plasma samples)

  • NDMAD (56.5% vs 97.1%)

  • NPYR (17.4% vs 91.2%)

Downregulation

  • Pyruvate; triphosphoglyceric acid

  • γ-aminobutyric acid; l-glutamic acid

  • Hypoxanthine; acetylcarnitine

  • Lysophosphatidic acid (20:4, 20:5)

  • Hemolytic phosphatidylserine (20:4, 22:6)

  • Hypoxanthine and xanthine metabolic pathways

  • Taurine and hypotaurine metabolic pathways

  • Arginine and proline metabolic pathways

  • The 2-oxocarboxylic acidmetabolic pathway

  • Alanine, aspartic acid, and glutamic acid metabolic pathways

  • Glyoxylic acid and dicarboxylic acid metabolic pathways

Upregulation

  • Itric acid; xanthuric acid

  • Lyso-phosphatidylcholine 16:1

  • 7-Methylguanosine; adenosine 5′-monophosphate

Esophageal squamous cell carcinoma (Zhao, 2021)Case-control studyHuman (plasma samples)

  • NDMA (0.245 vs 0.406 ng/ml)

  • NDBA (ND vs 0.094 ng/ml)

  • NDphA (ND vs 0.058 ng/ml)

  • NPyr (0.144 vs 0.30 ng/ml)

  • NDPA (ND∼0.064 vs ND∼0.182 ng/ml)

Downregulation

  • Sphingosine; tryptophan

  • Indole-3-acetic acid; serotonin

  • Alanine, aspartate, and glutamate metabolism

  • Phenylalanine metabolism

  • Arginine biosynthesis

  • d-Glutamine and d-glutamate metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

UpregulationDihydrosphingosine; sphingosine-1-phosphate; dihydrosphingosine-1-phosphate; quinolinic acid
Esophageal squamous cell carcinoma (Zhang et al., 2022a)Experimental StudyMalignant transformation Het-1a cellsMNNG (2 μmol/l)DownregulationCosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Linoleic acid metabolism

  • Arachidonic acid metabolism

  • Alpha-linolenic acid metabolism

  • Glycerophospholipid metabolism

Upregulation

  • Linoleate; hexadecanoic acid

  • Octadecanoic acid; arachidonate

Esophageal squamous cell carcinoma (Zhang et al., 2022c)Experimental StudyMice (serum and urine samples)

  • The nitrosamines mixture

  • Low dose group (7.5 ng/kg)

  • Medium dose group (3 μg/kg)

  • High dose group (1.2 mg/kg)

Downregulation

  • Palmitic acid; linoleic acid

  • y-Linoleic acid; arachidonic acid

  • Docosahexaenoic acid

  • Eicosapentaenoic acid

  • Biosynthesis of unsaturated fatty acids metabolism

  • Alpha-linolenic acid metabolism

  • Pentose phosphate metabolism

  • Glycerophospholipid metabolism

  • β-Alanine metabolism

  • Glutathione metabolism

  • Sphingolipid metabolism

UpregulationPalmitoylcarntine
Esophageal squamous cell carcinoma (Zhao et al., 2022a)Experimental StudyMice (serum samples)NMBA (0.4 mg/kg)Downregulation

  • Heptanoic acids; palmitic acid

  • Stearic acid; oleic acid

  • l-Palmitoylcarnitine; acetylcarnitine

  • Alanine, aspartate, and glutamate metabolism

  • Arginine and proline metabolism

  • Arginine biosynthesis

  • Nicotinate and nicotinamide metabolism

  • Sphingolipid metabolism

  • Tryptophan metabolism

Upregulation

  • Glycocholic acid; taurocholic acid

  • Sphingosine-1-phosphate

Hepatocellular carcinoma (Ding et al., 2020)Experimental StudyMice (liver tissues samples)DEN (100 mg/l DEN in drinking water)UpregulationProlineProline metabolic pathway
Bladder cancer (Afify et al., 2021)Experimental StudyMice (bladders tissues samples)BBN (0.05% in drinking water)Upregulation

  • Glycerphosphoethanolamine

  • Glycerphosphocholine

  • Glycerophosphoserine

  • Glycerophosphoglycerol

  • Lysophospholipids

  • TCA cycle

  • Fatty acid, dicarboxylate

  • Tryptophan metabolism

  • Glutamate metabolism

  • Purine metabolism

  • Phospholipid metabolism

Hepatocellular carcinoma (Yang et al., 2018)Experimental StudyMice (serum and urine samples)DEN (50 mg/kg DEN intraperitoneal injection)Downregulation

  • Leucine; isoleucine; valine; lactate

  • 3-Hydroxybutyrate; glutamine; glycine; formate

—
UpregulationAcetate; glutamate; tyrosine
Hepatocellular carcinoma (Wang et al., 2022)Experimental StudyMice (urine samples)DEN (60 mg/l DEN intraperitoneal injection)Upregulation

  • Hippurate; creatinine; putrescine

  • Choline; taurinedimethylglycine

  • Glycine, serine, and threonine metabolism

  • Taurine and hypotaurine metabolism

  • Arginine and proline metabolism

  • Primary bile acid biosynthesis

Hepatocellular carcinoma (Peng et al., 2015)Experimental StudyMice (liver tissues samples)DEN (80 mg/l DEN intraperitoneal injection)Downregulation

  • Lactate; palmitelaidic acid

  • Glycerol 3-phosphate; d-glucose

  • Amino acid metabolism (33.33%)

  • Carbohydrate metabolism (41.33%)

  • Lipids metabolism (21.33%)

  • Nucleotides metabolism (4.00%)

Upregulationl-glutamine; l-aspartate; malate
Hepatocellular carcinoma (Haberl et al., 2021)Experimental StudyMice (liver tissues samples)DEN (25 µg/g DEN intraperitoneal injection)Downregulation

  • Monounsaturated lysophosphatidylethanolamine

  • Monounsaturated phospholipids phosphatidylserine

  • Phosphatidylcholine (PC34:2, PC36:3, PC40:7)

—
Upregulation

  • Triglyceride

  • Cholesterol (16:0, 16:1, 18:1, 18:2, 20:4, 22:6)

  • Ceramide ((d18:1/16:0, d18:1/18:0, d18:1/20:0, d18:1/23:0, d18:1/24:1)

  • Monounsaturated phosphatidylinositol

—
Hepatocellular carcinoma (Chen et al., 2019)Experimental StudyMice (liver tissues samples)DEN (5 μg/g DEN intraperitoneal injection)Downregulationα-Glucose; β-glucose

  • Lipid metabolism

  • Amino acid metabolism

Upregulation

  • Lactate; creatine; acetate; valine; glutamate; alanine; lysine; histidine

  • Glutamine; glycine; glutathione

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