Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentaerythritol tetranitrate (PETN, NF) is a drug used to prevent angina pectoris. PETN without a lactose stabilizer is used as an explosive. NTP Toxicology and Carcinogenesis studies were conducted by administering PETN, NF, to groups of F344/N rats and B6C3F1 mice of each sex once by gavage or in feed for 14 days, 13 or 14 weeks, or 2 years. The PETN component was greater than 99% pure. Genetic toxicology studies were conducted with Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day and Thirteen-Week Studies: All rats and mice lived to the end of the 14-day studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats were comparable. The final mean body weight of female mice that received 50,000 ppm was 13% lower than that of controls. No clinical signs or toxic lesions were attributed to PETN, NF, administration. All rats and mice lived to the end of the 13-week (mice) and 14-week (rats) studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats and mice were similar, although weight gains of female rats at 25,000 and 50,000 ppm were less than that of controls. The nitrite level in urine of rats and methemoglobin levels in whole blood of rats and mice were not affected by administration of PETN, NF. An adenoma of the Zymbal gland was seen in a female rat that received 50,000 ppm. A hepatocellular adenoma was seen in a female mouse that received 50,000 ppm. Based on these results and the NTP convention of limiting concentrations in 2-year feed studies to 5% of the diet, the 2-year studies were conducted by administering 0, 25,000 or 50,000 ppm PETN, NF, in feed for 104 weeks to groups of 50 male rats and for 103 weeks to groups of 49 or 50 mice of each sex. Groups of 50 female rats were given feed containing 0, 6,200, or 12,500 ppm PETN, NF, for 104 weeks. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose male rats were 2%-9% lower than those of controls throughout the study; body weights of all groups of female rats were similar. No significant differences in survival were observed between any groups of rats of either sex (male: control, 23/50; low dose, 29/50; high dose, 29/50; female: 33/50; 33/50; 31/50). Mean body weights of dosed and control mice were similar. The survival of both groups of dosed male mice was significantly greater than that of the controls (26/49; 38/50; 38/50). No significant differences in survival were observed between any groups of female mice (38/50; 30/50; 38/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: No nonneoplastic lesions were attributed to PETN, NF, administration in rats or mice. Neoplasms of the Zymbal gland occurred in dosed male (control, 0/49; low dose, 3/45; high dose, 2/41) and dosed female (0/36; 1/37; 3/35) rats. The historical incidence of these neoplasms is 1% +/- 2% in untreated males and 0.6% +/- 1% in females. At no site was a significantly increased incidence of neoplasms observed in dosed male or female mice. Genetic Toxicology: PETN, NF, was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 when tested with or without exogenous metabolic activation (S9). When tested for cytogenetic effects in cultured CHO cells, PETN, NF, induced sister chromatid exchanges (SCEs) in the presence and absence of metabolic activation; no induction of chromosomal aberrations was observed in CHO cells with or without activation. Audit: The data, documents, and pathology materials from the 2-year studies of PETN, NF, have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year feed studies, there was equivocal evidence of carcinogenic activity of PETN, NF, for male and female F344/N rats, based on a marginal increase in neoplasms of the Zymbal gland. Female rats might have tolerated a higher dose. There was no evidence of carcinogenic activity of PETN, NF, forher dose. There was no evidence of carcinogenic activity of PETN, NF, for male or female B6C3F1 mice fed diets containing 25,000, or 50,000 ppm for 2 years. No nonneoplastic lesions were attributed to PETN, NF, administration. Synonyms for PETN: 2,2-bis((nitrooxy)methyl)-1,3-propanediol dinitrate (ester); 2,2-bisdihydroxy-methyl-1,3-propanediol tetranitrate; niperyt; nitropentaerythritol; pentaerythrityl tetranitrate; penthrit Trade Names for PETN, NF: Angitet; Cardiacap; Dilcoran-80; Dipentrate; Hasethrol; Lentrat; Metranil; Mycardol; Neo-Corovas; Nitropenta; Nitropenton; Pentafin; Pentanitrine; Pentitrate; Pentral 80; Pentrite; Pentritol; Pentryate; Peridex; Pergitral; Peritrate; Perityl; Prevangor; Quintrate; Subicard; Terpate; Vasodiatol
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Pentaerythritol Tetranitrate (CAS No. 78-11-5) with 80% D-Lactose Monohydrate (PETN, NF) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1269 39

The aim of the present study was to comparatively evaluate DNA damage and cellular death in cells exposed to various commercially available mouthrinses: Listerine Cepacol, Plax alcohol free, Periogard, and Plax Whitening. A total of 75 volunteers were included in the search distributed into five groups containing 15 people each for in vivo study. Exfoliated buccal mucosa cells were collected immediately before mouthrinse exposure and after 2 weeks. Furthermore, blood samples were obtained from three healthy donors for in vitro study. The micronucleus test was used to evaluate mutagenicity and cytotoxicity in vivo. The single-cell gel (comet) assay was used to determine DNA damage in vitro. After 2 weeks exposure, Periogard showed 1.8% of micronucleated cells with significant statistical differences (p < 0.05) compared to before exposure (0.27%). Plax Whitening presented high tail moment value (4.5) when compared to negative control (0.6). The addition of all mouthrinses to cells incubated with methyl methanesulfonate did not alter the number of strand breaks in the genetic material. Listerine was able to reduce genetic damage induced by hydrogen peroxide because a decrease of tail moment was noticed. The results of the present study suggest that Periogard and Plax Whitening can induce genetic damage, whereas Listerine is an antioxidant agent. Since DNA damage is considered to be prime mechanism during chemical carcinogenesis, these data may be relevant in risk assessment for protecting human health and preventing carcinogenesis.
 ...
PMID:Cytogenetic damage induced by mouthrinses formulations in vivo and in vitro. 2154 72