Mammary Carcinomas Induced in Human c‐Ha‐<i>ras</i> Proto‐oncogene Transgenic Rats Are Estrogen‐independent, but Responsive to <i>d</i>‐Limonene Treatment

Asamoto, Makoto; Ota, Tomohiro; Toriyama‐Baba, Hiroyasu; Hokaiwado, Naomi; Naito, Akira; Tsuda, Hiroyuki

doi:10.1111/j.1349-7006.2002.tb01197.x

Cited by 35 publications

(31 citation statements)

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“…32) This is in line with a report that sarcomas were observed in ovariectomized female rats treated with DMBA. 35) The lack of sarcomas in Hras128 rats undergoing ovariectomy after MNU administration 27) may be due to the drastic decrease in tumor yield caused by the reduction in TEB number and also the short duration of the experiment. It should be borne in mind, however, that since Rastransformed mammary epithelial cells exhibit a spindle-shaped morphology upon exposure to TGF-β1 36) and this latter is induced by androgen in vivo, 37) an alternative explanation exists for mixed epithelial-mesenchymal elements being limited to male rats.…”

Section: Discussionmentioning

confidence: 99%

Preferential mammary carcinogenic effects of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in human c‐Ha‐ras proto‐oncogene transgenic rats

et al. 2004

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he Ras family is composed of three members, Harvey Ras, Kirsten Ras and N-Ras, which exhibit mutations at variable frequencies in various human and animal tumors, 1) with involvement appearing to be tissue-specific. 2, 3) For example, with N-methyl-N-nitrosourea (MNU) in experimental animals, Haras mutations are found primarily in mammary tumors, [4][5][6] while colon tumors generally have Ki-ras mutations. 7) In humans, Ki-ras mutations are preferentially found in colon, 8,9) pancreatic duct 10) and bile duct carcinomas, 11) and N-ras mutations are typically seen in myeloid leukemia. 12) We have generated a transgenic rat line, harboring copies of a human c-Ha-ras proto-oncogene (Hras128 rat), and have shown that these animals are highly susceptible to mammary, 13,14) bladder 15) and esophageal 16) carcinogens.Heterocyclic amines found in overcooked foods are both mutagenic and carcinogenic to animals, 17) and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), the most abundant in our daily diet, 18) has been shown to induce primarily colon, mammary and prostate tumors in rats. [19][20][21] PhIP intake in food has also been implicated as an important risk factor in humans 22,23) although further analysis of the interactions between PhIP and relevant macromolecules is required for a full understanding of the carcinogenic processes.Although mutational analyses of tumors induced by PhIP have been conducted, 24) specific molecular targets have yet to be elucidated. One problem is that the relatively weak carcinogenic potential requires the use of long experimental periods for lesion induction. This study was conducted to analyze the susceptibility of Hras128 rats to PhIP, in the hope of overcoming the above problem. We show here that Hras128 rats are in fact highly susceptible to PhIP mammary carcinogenesis, and multiple tumors of various morphological types develop in a short period. Furthermore, they feature mutations of the transgene along with down-regulation of BRCA1. Materials and MethodsAnimals and experimental protocol. Seven-week-old Hras128 rats of both sexes were maintained on basal diet (Oriental MF, Oriental Yeast Co., Ltd. Tokyo) with tap water ad libitum under standard conditions. 13) Seven females and 18 males were treated with PhIP HCl salt (NARD Institute, Osaka), at doses of 100 mg and 80 mg/kg body weight, respectively, by gastric intubation, from 3 to 4 times a week over a 9-week period (total, 8 times in females and 10 times in males). Five female and 20 male Hras128 rats were similarly treated with vehicle (saline). Sacrifice was at week 12 for females and week 30 for males. Seven female and 20 male wild-type littermates were also treated with PhIP, and 8 female and 20 male wild-type littermates received the vehicle (saline).The experiments were conducted according to the "Guidelines for Animal Experiments in the National Cancer Center Japan" promulgated by the Committee for Ethics of Animal Experimentation.Tissue preparation. Immediately after killing of the animals, mammary tumors wer...

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Section: Discussionmentioning

confidence: 99%

Preferential mammary carcinogenic effects of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in human c‐Ha‐ras proto‐oncogene transgenic rats

et al. 2004

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“…For example, D-limonene, as one of the bioactive components in PCRV and PCR volatile oils, showing the ability to the increase the expectoration rate and possess anticancer activities (Asamoto et al, 2002;Bezerra, Costa, & Nogueira, 2013;Shen, 2002). Significant antimicrobial activity of a-terpineol has also been proved (Carson & Riley, 1995;Cosentino et al, 1999).…”

Section: Introductionmentioning

confidence: 98%

Chemical features of Pericarpium Citri Reticulatae and Pericarpium Citri Reticulatae Viride revealed by GC–MS metabolomics analysis

Dong

Shao

et al. 2015

Food Chemistry

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“…The essential oils are their bioactive constituents. For example, D-limonene, as one of the main bioactive components in all of their volatile oils, has been reported to make the expectoration easy and possess anticancer activity [1,3]. Up to now, to the best of our knowledge, there is no systematic comparative study on volatile oils of ACR, CCR, FCR, ECG, PCRV and PCR.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of volatile constituents in Citrus Reticulata Blanco using GC–MS and alternative moving window factor analysis

Liu

et al. 2009

J of Separation Science

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The similarities and differences of essential oil components in Album Citri Reticulatae (ACR), Cylindricae Citri Reticulatae (CCR), Folium Citri Reticulatae (FCR), Exocarpium Citri Grandis (ECG), Pericarpium Citri Reticulatae Viride (PCRV) and Pericarpium Citri Reticulatae (PCR) were investigated by GC–MS combined with a chemometric method named alternative moving window factor analysis (AMWFA). And temperature‐programmed retention indices (PTRIs) were used together with mass spectra for identification of the essential oil components. In essential oils of ACR, CCR, FCR, ECG, PCRV and PCR, 28, 26, 61, 62, 52 and 48 components were determined representing 93.13, 94.44, 93.53, 87.67, 99.03 and 98.03% of the total relative content, respectively. Also, the essential oils significantly differed both qualitatively and quantitatively. There were 14 common components among ACR, CCR, FCR, ECG, PCRV and PCR, their abundance varied in the ranges from 32.39% in FCR to 94.66% in PCRV. The results obtained may be helpful to the further study of pharmacological activity for their potential utilization as therapeutical agents.

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Mammary Carcinomas Induced in Human c‐Ha‐ras Proto‐oncogene Transgenic Rats Are Estrogen‐independent, but Responsive to d‐Limonene Treatment

Cited by 35 publications

References 16 publications

Preferential mammary carcinogenic effects of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in human c‐Ha‐ras proto‐oncogene transgenic rats

Preferential mammary carcinogenic effects of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in human c‐Ha‐ras proto‐oncogene transgenic rats

Chemical features of Pericarpium Citri Reticulatae and Pericarpium Citri Reticulatae Viride revealed by GC–MS metabolomics analysis

Comparative analysis of volatile constituents in Citrus Reticulata Blanco using GC–MS and alternative moving window factor analysis

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