Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00249 (Mutagen)
 5,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (TFPB), 1-benzoyl-2-trifluoromethyl-2-acetoxyethene (BTAE), and 1-benzoyl-2-trifluoromethyl-2-(4-methylthio)benzoyloxyethene (BTME), were synthesized and investigated for inhibition of tRNA binding by N-acetoxy-2-acetylaminofluorene (N-AcO-AAF), and induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver by 2-acetylaminofluorene (2-AAF). Male F344 rats were given BTAE or BTME intraperitoneally and 2-AAF by intragastric intubation. Two weeks following the treatment, the rats were maintained on the diet containing 0.05% phenobarbital for an additional 6 weeks and then killed. Development of GST-P positive foci was not affected by concomitant treatment with BTAE or BTME. These two compounds inhibited the in vitro binding of N-AcO-AAF to tRNA. Thus, although these diacylmethane derivatives had the in vitro inhibitory activity, they did not inhibit tumor-initiating activity of 2-AAF in the rat liver.
Teratog Carcinog Mutagen 1992
PMID:Effect of acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione on 2-acetylaminofluorene-induced glutathione S-transferase positive foci in the rat liver. 136 64

Eight pesticides were tested in a medium-term bioassay based upon the induction of preneoplastic lesions in the liver. Rats were initially given diethylnitrosamine intraperitoneally at a dose of 200 mg/kg body weight and 2 weeks later were treated with the pesticides for 6 weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione S-transferase placental form positive foci in the liver with those of controls given diethylnitrosamine (DEN) alone. Positive results were seen with p,p-DDT and Triadimefon. Permethrin (mixture of 39% cis form and 61% trans form) showed borderline results. Permethrin (25/75), Deltamethrin, Cypermethrin (52/48), while Trimorphamide and Propineb gave negative results. Our findings provide experimental evidence to indicate that compounds active in this assay have a potential for liver carcinogenicity in rodents.
Teratog Carcinog Mutagen 1992
PMID:Analysis of carcinogenic activity of some pesticides in a medium-term liver bioassay in the rat. 136 65

Initiating activity of N-nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8-weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1,600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose-dependent initiating activity of NDELA was observed in terms of development of glutathione S-transferase placental form (GST-P) positive liver cell foci, this being more apparent with PB promotion than with 2-AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work.
Teratog Carcinog Mutagen 1991
PMID:Dose response study of N-nitrosodiethanolamine initiation of rat hepatocarcinogenesis. 168 2

The modifying potential of prior administration of toxic agents was investigated in our multi-organ carcinogenesis model using male F344/DuCrj rats with the aim of assessing the link between tissue damage and initiation. Animals were administered one of four toxic agents for 8 wk, and then treated with N-diethylnitrosamine (DEN, 100 mg/kg body weight (b.w.), intraperitoneally (i.p.), single injection), N-methylnitrosourea (MNU, 20 mg/kg b.w., i.p., four times during wk 9 and 10), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, during wk 11 and 12) for multi-organ carcinogenesis. All surviving rats were killed at the end of wk 36, and the major organs carefully examined for preneoplastic and neoplastic lesion development. Immunohistochemical demonstration of glutathione S-transferase placental form (GST-P) positive foci was also performed to facilitate quantitative assessment of liver lesion development. D-galactosamine (300 mg/kg b.w., i.p., once a week), a hepatotoxin, significantly inhibited the induction of GST-P positive foci, while 4,4'-diaminodiphenylmethane (DDPM, 0.1% in diet), a bile duct proliferator which is itself a hepatocarcinogen, possessed enhancing activity. DDPM, also a goitrogen, clearly inhibited the development of follicular cell tumors in the thyroid. Uracil (3.0% in diet), which is an inducer of papillomatosis in the urinary bladder, did not exert any enhancing potential on bladder carcinogenesis. Bleomycin (2 mg/kg b.w., i.p., twice a week), which is an alveolar epithelium injuring agent, also did not modify the induction of alveolar epithelium proliferative lesions. These results indicate that prior organ injury by toxic agents does not always act to enhance sensitivity to carcinogenesis.
Teratog Carcinog Mutagen 1993
PMID:Modifying influence of prior treatment with toxic agents on induction of preneoplastic and neoplastic lesions in a medium-term multi-organ carcinogenesis bioassay. 750 56

Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic potential that have not thus far been extensively explored from the pharmacogenetic standpoint, are also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise from environmental chemicals.
Environ Mol Mutagen 1995
PMID:Influence of heredity on human sensitivity to environmental chemicals. 778 56

This paper evaluates the potential effects of arecanut (Areca catechu, L.), an important ingredient of betel quid, on the garlic (Allium sativum, L.)-modulated activities of hepatic detoxication system enzymes, acid soluble sulfhydryl content, and lipid peroxidation in mice. Mice were fed on either a normal diet or a diet containing 0.25%, 0.5%, or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment oral administration of garlic at the dose level of 20 or 100 mg/kg body weight/day was supplemented. Significant modulation in the activities of phase I and phase II enzymes, -SH content, and malondialdehyde (MDA) level by garlic was observed. Garlic-modulated alterations in glutathione S-transferase (GST) activity and -SH content were decreased, while cytochrome b5, cytochrome P-450, and MDA levels were further augmented by the arecanut plus garlic treatments.
Teratog Carcinog Mutagen 1995
PMID:Evaluation of the modifying influence of arecanut on the garlic-modulated hepatic detoxication system enzymes, sulfhydryl content, and lipid peroxidation in mice. 858 84

The modulatory influence of arecanut, a masticatory in several human populations, on the levels of biotransformation system enzymes in mouse liver has been studied. Swiss albino mice of either sex (4 weeks old) were fed on diets containing 0.25%, 0.5%, or 1% arecanut (w/w) for 5 weeks. In addition, a group of mice received a 1% arecanut diet for 36 weeks. The findings revealed a significant increase in hepatic levels of cytochrome b5, cytochrome P-450, malondialdehyde (MDA), and glutathione S-transferase (GST). The hepatic -SH content was depressed by 0.5% and 1% arecanut diets. Long-term feeding of a 1% arecanut diet elicited changes similar to those seen following treatment for 5 weeks. Arecanut-modulated profiles of biotransformation enzymes and antioxidant levels are suggestive of its influence in the process of carcinogenesis induced by bioactivated electrophilic species of potential chemical carcinogens among habitual arecanut chewers. Arecanut was also tested for its potency either to induce or to alter 7,12-dimethylbenz[a]anthracene (DMBA)-induced papillomagenesis in the skin of the mouse. Animals put on a 1% arecanut diet and treated with a standard two-stage protocol for tumor induction developed a 5.41 tumor burden (control value: 5.76) along with 100% incidence of mice bearing papillomas (control value: 94.4%), thus signifying that dietary intake of 1% arecanut for 18 weeks could not induce/alter the mouse skin tumorigenesis pattern.
Teratog Carcinog Mutagen 1995
PMID:Modulatory influence of arecanut on the mouse hepatic xenobiotic detoxication system and skin papillomagenesis. 858 85

The carcinogenicity of daminozide (succinic acid-2,2-dimethylhydrazide; Alar), a plant growth regulator used primarily in apple orchards, has been the subject of recent investigations by several national and international organizations because of contradictory study results. The aim of the present study was to assess the carcinogenicity of daminozide alone and in combination with 1,1-dimethylhydrazine (UDMH), its major contaminant, in a novel medium-term bioassay in Fischer 344 rats, the DEN-PH model. Rats were given diethylnitrosamine (DEN) at 200 mg/kg body weight intraperitoneally and then 2 weeks later were given daminozide at 20,000 ppm or daminozide plus UDMH at 75, 150, or 300 ppm in the diet for 6 weeks and were then killed; all rats underwent a partial (two-thirds) hepatectomy (PH) at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of preneoplastic foci positive for the glutathione S-transferase placental form (GST-P+) in the liver of treated rats, with those in controls given DEN alone. Daminozide, UDMH, and the combination were not carcinogenic in this model. This novel medium-term bioassay for carcinogenicity is considered to be practical for the rapid evaluation of both agrochemical formulations and contaminants found in agrochemicals and other compounds.
Teratog Carcinog Mutagen
PMID:Lack of carcinogenicity of daminozide, alone or in combination with its contaminant 1,1-dimethylhydrazine, in a medium-term bioassay. 873 81

Four pesticides were examined for hepatopromoting activity using a medium-term bioassay based upon induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN; 200 mg/kg body weight) intraperitoneally and 2 weeks later were treated with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN; 75 and 150 ppm), diazinon (500 and 1,000 ppm), phenthoate (500 and 1,000 ppm), or iprobenfos (500 and 1,000 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. All of the pesticides gave negative results, the numbers and areas of GST-P positive foci not exceeding the control values for animals given DEN alone. Indeed, a significant reduction of foci development was seen for EPN (75 ppm). These findings provide experimental evidence that the presently examined four pesticides do not have hepatocarcinogenic potential in rats.
Teratog Carcinog Mutagen 1995
PMID:Lack of promoting activity of four pesticides on induction of preneoplastic liver cell foci in rats. 886 80

The present study evaluates the potential of arecoline alkaloid on chlorophyllin (CHL) modulated levels of hepatic biotransformation system enzymes in suckling neonate and lactating mice. CHL [50, 100, or 200 mg/kg body weight (b.w.)/day] induced significant increases in the hepatic levels of glutathione S-transferase (GST) and sulfhydryl (-SH) in lactating dams and suckling pups of 14 or 21 days. The depleted level of hepatic Cytochrome (Cyt.) P-450 was observed only in lactating dams given 200 mg/kg b.w. CHL. Arecoline (20 mg/kg b.w.) could depress the CHL-induced levels of hepatic GST and -SH, while Cyt. P-450 and Cyt. b5 levels remained unaltered by arecoline alone or arecoline plus CHL treatment. In lactating dams the modulated levels of hepatic biotransformation system enzymes potentially could affect the detoxication efficacy of administered chemicals besides influencing the rate and extent of passage of metabolites to suckling neonate.
Teratog Carcinog Mutagen 1996
PMID:Postnatal effect of arecoline on chlorophyllin-modulated hepatic biotransformation system enzymes in suckling neonate and lactating mice. 887 39


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