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

In a previous study in rats we have shown that castration prior to weekly administration of N-nitrosobis(2-oxopropyl)amine (BOP) prevents induction of nasal and paranasal cavity (NPNC) tumors, indicating androgen dependency of these neoplasms. To investigate the possible inhibitory effect of testosterone withdrawal on the growth of NPNC tumors, in the present study rats were castrated following weekly treatment with BOP for 10, 20 or 30 weeks. This treatment did not alter the incidence, type, location, latency or multiplicity of NPNC tumors. However, simultaneous treatment of castrated rats with BOP and testosterone (T) yielded NPNC tumors in an incidence and patterns comparable to that seen in BOP-treated intact and BOP-plus-T-treated intact rats. Serological examination revealed abnormally high levels of T and 17-beta estradiol (E) in rats, which were killed immediately after 10, 20 or 30 weekly BOP administrations. The overall results suggest that the initiation but not the promotional stage of NPNC carcinogenesis is governed by androgens.
Carcinogenesis 1988 Aug
PMID:The role of testosterone in the nasal cavity tumors induced by N-nitrosobis(2-oxopropyl)amine in rats. 340 38

Detailed histologic observations were performed on the head of the pancreas of hamsters treated with 10 mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) once a week for 6 weeks with or without cholecystectomy. Cholecystectomy was performed 5 weeks before starting BOP initiation. The incidence of head cancers was 100% and cholecystectomy did not affect pancreatic carcinogenesis by BOP. Common bile duct dilatation was produced by advanced pancreatic head carcinomas and microadenocarcinomas in common duct. Micro-adenocarcinomas were not macroscopically detected since the tumors were located in the lumen of common duct.
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PMID:Common duct carcinoma and obstruction in female hamsters treated with N-nitrosobis(2-oxopropyl)amine and/or cholecystectomy. 343 6

In studies designed to determine the influence of dietary Se on pancreatic carcinogenesis, Syrian golden hamsters were fed unsupplemented torula yeast diet or diet supplemented with 0.1 or 5.0 ppm Se, from sodium selenite, starting at 4 weeks of age until the termination of the study. In separate groups, hamsters were given the diet supplemented with 0.1 ppm Se until 5 days after carcinogen treatment. Then they were fed either the unsupplemented diet or the diet supplemented with 5.0 ppm Se until the end of the experiment. N-Nitrosobis(2-oxopropyl)amine (BOP; CAS; 60599-38-4) treatment was given as a single sc injection of 20 mg/kg (body wt) at 8 weeks of age, and surviving hamsters were killed 50 weeks later. As a measure of Se status, glutathione peroxidase (GSHPX) activities were determined in plasma, erythrocytes, and liver. Values were elevated in animals fed higher levels of dietary Se. BOP treatment depressed plasma GSHPX at 24 hours and elevated erythrocyte and liver values at 4 weeks. Pancreatic ductular adenoma yields were inhibited with each elevation of dietary Se in female hamsters fed the diets, both before and after BOP administration, and were further inhibited in females that were fed diets containing 0.1 ppm Se before BOP administration and that were changed to the unsupplemented or 5.0-ppm-supplemented diets after BOP was given. Pancreatic ductular adenoma yields were highest in all male groups given diets of 0.1 ppm Se before BOP administration, irrespective of the Se level after BOP was fed. Adenoma yields in males were lowest in hamsters fed unsupplemented diet, both before and after BOP treatment. Pancreatic carcinoma yields were low and not influenced by dietary Se. The incidence of hepatic necrosis was elevated in BOP-treated hamsters fed the unsupplemented diet, and that of biliary cystic adenomas was highest in the group fed 0.1 ppm Se before and after BOP treatment.
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PMID:Effects of dietary selenium on bis(2-oxopropyl)nitrosamine-induced carcinogenesis in Syrian golden hamsters. 346 17

The effect of exogenous secretin on pancreatic carcinogenesis in WO strain hamsters has been examined in the nitrosamine-ductular adenocarcinoma model. Secretin, 20 clinical U/kg, stimulated a maximal secretory response of pancreatic juice and bicarbonate when given iv. The same dose given sc for 6 weeks had no significant effect on pancreatic wet weight and DNA or RNA contents. However, when given to animals receiving N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4] (5 mg/kg), it reduced the latency and increased the induction rate of tumor development when compared with the carcinogen given alone to animals (secretin + BOP, 15 of 17 animals with tumors; BOP alone, 4 of 13 with tumors at 15 wk; P less than .002). These effects are consistent with secretin acting as a cocarcinogen in this model of pancreatic carcinogenesis.
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PMID:Pancreatic carcinogenesis: effect of secretin in the hamster- nitrosamine model. 346 21

Studies were conducted to evaluate the ability of dietary dried cabbage supplements to inhibit pancreatic carcinogenesis in hamsters and skin tumorigenesis in mice. Pancreatic cancer was induced by treatment with 40 mg/kg body wt N-nitrosobis-(2-oxopropyl)amine (BOP). Cabbage was fed from before carcinogen treatment in low fat diet and, beginning 1 week after BOP treatment, cabbage was given in low fat and high fat diets in comparison with the respective non-cabbage-containing diets. Dried cabbage was incorporated at 9 and 11% levels into the low and high fat diets. Feeding cabbage in the high fat diet elevated the yield of BOP-induced pancreatic ductular carcinoma (1.6 carcinomas/effective animal) in comparison with that observed in hamsters fed cabbage in a low fat diet or in those given a high fat diet without cabbage, 0.6-0.8 carcinomas/effective animal (P less than 0.05). Furthermore, the incidence of BOP-induced gall bladder adenocarcinoma was elevated in cabbage-fed hamsters irrespective of dietary fat intake. Effects of dietary fat and cabbage on food consumption, body weight, and serum T3 and T4 values are described. Skin tumorigenesis was induced in SENCAR mice by 10 nmol 7,12 dimethylbenz[a]anthracene (DMBA) and promoted beginning 1 week later with twice weekly applications of 2 micrograms 12-O-tetradecanoyl-13-phorbol acetate (TPA). Dried cabbage was incorporated into AIN semi-purified diets from before DMBA treatment and throughout TPA treatment. Skin papilloma yield was elevated in DMBA-initiated TPA-promoted mice that were fed diets containing 10% cabbage. Mice fed cabbage developed an average of 8.45 papillomas per mouse following 22 weeks of promotion while mice given control diet developed 7.25 papillomas per mouse (P less than 0.001). Cabbage feeding did not influence survival, food consumption or body weight of the mice. These results suggest the need for further research on the use of cabbage as a chemopreventive measure.
Carcinogenesis 1987 Jul
PMID:Enhanced pancreatic and skin tumorigenesis in cabbage-fed hamsters and mice. 359 24

The early putative pre-neoplastic lesions which arise in the Syrian golden hamster pancreas prior to the appearance of carcinomas following treatment with N-nitrosobis(2-oxopropyl)amine (BOP), have been characterized and quantitated in order to refine a protocol which permits post-initiation modulation to be evaluated within a relatively short period of time. The proposed 4-month protocol was used to investigate the modulating effects of dietary saturated fat on pancreatic carcinogenesis in hamsters. Hamsters were injected s.c. with 20 mg BOP/kg body wt at 5, 6 and 7 weeks of age. The animals were fed a low fat (LF) control diet (5% lard) or a high fat (HF) diet (20% lard) subsequent to the initiation protocol. At 4 months post-initiation, the pancreata were quantitatively examined for the number and size of putative pre-neoplastic lesions. The major attention was directed to intraductal epithelial hyperplasia of inter/intralobular or main ducts, cystic ductal complexes, tubular ductal complexes and ductal complexes that seemed to be intermediate between the latter two. The number of large ductal complexes of the intermediate and tubular category was significantly greater in hamsters fed a diet with 20% saturated fat as compared to animals maintained on 5% saturated fat. Furthermore, the number of ducts with intraductal hyperplasia was greater in the high fat group, and the proportion of such lesions judged to show atypia was also higher in this group. Dietary fat did not have a significant effect on either the cystic ductal complexes or the incidence of hyperplasia in the main pancreatic duct. These results suggest that a diet high in saturated fat enhances pancreatic carcinogenesis in the BOP-hamster model and, moreover, they suggest that a short-term (4-month) protocol may be useful for evaluation of the effects of potential modulating factors on pancreatic carcinogenesis in Syrian golden hamsters. The utility of the approach should be further evaluated and correlated with the results of long-term studies.
Carcinogenesis 1987 Jun
PMID:Characterization of a 4-month protocol for the quantitation of BOP-induced lesions in hamster pancreas and its application in studying the effect of dietary fat. 360 81

The metabolism of N-nitrosobis(2-oxopropyl)amine (BOP) was examined in microsomes from uninduced F-344 rats. Even when the conditions were varied, no metabolism of this compound was detected. On the other hand, freshly isolated hepatocytes from F-344 rats metabolized BOP efficiently to CO2. The kinetics of conversion showed there were at least two components. The high affinity component had a Km of 0.13 mM while the lower had a Km of 1.3 mM. As products of the metabolism, N-nitroso(2-hydroxypropyl)(2-oxopropyl)-amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP) were found whereas little acetol and no N-nitrosomethyl-2-oxopropylamine (MOP) were detected.
Carcinogenesis 1987 Aug
PMID:The metabolism of N-nitrosobis(2-oxopropyl)amine by microsomes and hepatocytes from Fischer 344 rats. 360 90

The effect of exogenous testosterone on prostatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in intact and castrated rats was examined in Wistar-derived MRC rats. Daily administration of BOP (either s.c. or i.g.) for 3 days, at a dose of 20 mg/kg b.w. at the heights of prostatic cell proliferation induced by testosterone, led to development of a large number of prostatic tumors, the incidence of which, however, was dependent on the duration of testosterone administration. Testosterone given for life following BOP administration induced prostatic cancer in over 60% of rats, regardless of whether BOP was given orally or s.c., or whether the rats were orchiectomized or not, whereas tumor incidence was significantly lower in rats treated with testosterone for only a short period of time. One (3%) orchiectomized rat, which received testosterone only during BOP treatment, and four (15%) of rats treated with testosterone only for life also developed carcinomas. Histologically, a large number of BOP + testosterone-induced prostatic tumors were adenocarcinomas of various histological patterns and arose primarily from the dorsal lobe, whereas the great majority of squamous cell carcinomas were found in the ventral lobe. Simultaneously induced tumors were papillomas and carcinomas of the urinary bladder and urethra. Testosterone appeared to enhance the incidence of urinary bladder tumors, but not of the urethral tumors, whereas orchiectomy inhibited urethral carcinogenesis, and, to much lesser extent, urinary bladder tumor development. Rats treated weekly for 20 weeks with BOP (10 mg/kg/week i.g.) did not develop any prostatic tumors and all rats died of rectal cancer. Of rats treated similarly with BOP and with testosterone pellets for life following the last injection of BOP, 17% of rats developed prostatic cancer, all of the squamous cell type. Simultaneous testosterone and BOP treatment for 20 weeks followed by testosterone pellets for life resulted in a 39% tumor incidence (three adenocarcinomas, one anaplastic carcinoma, and five squamous cell carcinomas). The overall results suggest that testosterone plays an important role in the initiation of prostatic carcinogenesis, whereas the promotional phase is governed by the interaction of testosterone with other factors.
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PMID:Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N-nitrosobis(2-oxopropyl)amine. 366 75

N.m.r. spectroscopy demonstrates that N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) exists as a mixture of four isomers, A, B, C and D, the equilibrium ratios of which are 57:8:16:19, respectively, at 25 degrees C. Two of these isomers, A and B, are rotomers of the open chain conformer, while the other two, C and D, are rotomers of the ring tautomer of HPOP and are derived from A and B, respectively, via an intramolecular cyclization reaction. A syn orientation of the nitroso and carbonyl groups favors an open chain configuration (isomer A), while an anti orientation favors cyclization of the molecule (isomer D). Two forms of HPOP (I and II) which are mixtures of isomers A and C, and D and B, respectively were separated chromatographically. These two forms interconvert to each other. The first rate order constants for the interconversion reactions were determined to be 4.7 X 10(-3) and 12.8 X 10(-3)/min, respectively. During these reactions isomers A and D interconvert via the intermediate formation of isomer C. This suggests that rotomerization of C and D is thermodynamically more favorable than rotomerization of their open-chain tautomers A and B, and suggests an intramolecular interaction between the carbonyl and nitroso groups. Isomers A and D are formed during the metabolism of N-nitrosobis(2-oxopropyl)amine (BOP) and cis N-nitroso-2,6-dimethylmorpholine (NNDM), respectively, by hamster liver microsomes and NADH or NADPH. The stereo-specificity of reduction of BOP and the hydroxylation of cis NNDM results in the formation of two slowly interconvertible isomers of HPOP. This, in combination with a possible different metabolic fate of the cyclic and open tautomers of this compound, may have a significant impact on the mechanism of activation of pancreatropic nitrosamines which share HPOP as a common metabolite.
Carcinogenesis 1987 Jan
PMID:Structural relationships of pancreatic nitrosamine carcinogens. 380 97

Hamsters and rats metabolize [1-14C]N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitrosobis(2-oxopropyl)amine (BOP) to yield N-nitrosobis(2-hydroxypropyl)-amine (BHP), glucuronic acid conjugates of HPOP and BHP, the sulfate ester of HPOP and 14C-labeled urea, all of which are excreted, and 14CO2 which is both incorporated in the urea cycle, and exhaled. The extent of metabolism and the ratios of these metabolites does not vary significantly with age or sex of the animal, however, marked species differences are evident in the metabolite composition of urine 6 h following administration of HPOP. Hamsters sulfate HPOP several times more rapidly, and reduce it to BHP more efficiently than rats. In contrast, the rat excretes more unchanged HPOP and its glucuronic acid conjugate than the hamster. Since sulfation and glucuronidation of HPOP may be involved in its activation and detoxication, these reactions were examined in detail in order to elucidate the reason(s) for their distinctively different contributions to its metabolism in rats and hamsters. Conjugation of HPOP with glucuronic acid and sulfate occurs in the livers of both rats and hamsters and is catalyzed by microsomal glucuronyl transferases and cytosolic sulfotransferases, respectively. The levels of glucuronyl transferase activity for conjugating phenolic compounds are comparable in the livers of two species; however, glucuronidation of HPOP is catalyzed by an isozyme the activity of which is three times greater in rat than in the hamster. In contrast to glucuronidation, sulfation of HPOP is catalyzed approximately 10 times faster by hamster than rat liver cytosol. Although rat liver can catalyze sulfation of phenolic compounds very effectively, it has low activity in sulfating aliphatic alcohols and beta-hydroxynitrosamines. Since both aliphatic alcohols and HPOP are sulfated by hamster liver cytosolic preparations and since these reactions are not significantly affected by the classic phenol sulfotransferase inhibitors, it appears that beta-hydroxynitrosamines may be sulfated by the aliphatic (hydroxysteroid) sulfotransferase isozymes. The failure of the rat to extensively sulfate HPOP in vivo may be attributed to the high Km of rat hydroxysteroid sulfotransferases for this compound. Of the four isomers of HPOP, only isomer A, in which the nitroso group is syn to the free keto group, is sulfated in vitro to an appreciable extent. The other three isomers either are not sulfated, or become unstable and decompose when they undergo such a reaction.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1987 Feb
PMID:Species differences in the metabolism of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine. 380 15


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