• Title, Summary, Keyword: 7,12-dimethylbenz(${\alpha}$)anthracene

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Pre-initiation treatment of indole-3-carbinol(I3C) inhibits 7,12-Dimethylbenz[α] anthracene(DMBA)-induced rat mammary carcinogenesis (Indole-3-carbinol(I3C) 투여에 의한 7,12-Dimethylbenz[α] anthracene(DMBA) 유발 랫드 유선발암 억제)

  • Kang, Jin Seok;Ahn, Byeongwoo;Nam, Ki Taek;Choi, Mina;Kim, Ji Young;Kim, Dae Joong;Jang, Dong Deuk;Yang, Ki-Hwa
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.549-555
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    • 2001
  • Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

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Morphological Changes in the Mammary Organ Culture of the Rat Treated with 7,12-Dimethylbenz[$\alpha$]anthracene and N-methyl-N-nitrosourea (7,12-Dimethylbenz[$\alpha$anthracene 및 N-methyl-N-nitrosourea를 투여한 랫드 유선 조직 배양에 대한 형태학적 변화)

  • 문지영;정자영;김옥희;이형환
    • Toxicological Research
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    • v.16 no.4
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    • pp.275-284
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    • 2000
  • The organ culture model of the whole mammary gland has many advantages for the study of branching morphogenesis and biological characteristics, including tumorigenesis. Prior to whole gland organ culture, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or N-methyl-N-nitrosourea (MNU) for one week. The tramdorming effect and the morphological changes were assessed by the whole mount preparations and histopathological examination in terminal end buds (TEB), terminal ducts (TD), alveolar buds (AB), alveolar lobules (AL) and hyperplastic alveolar nodules (HAN) of the mammary gland. Grossfindings of the mammary glands at dissection were higher branching morphogenesis and larger volume in carcinogen-treated groups than in carcinogen-non-treated groups. Results of the whole mount method were coincided with those of the histopathological observations. Circular TEB, normally maintained AB, AL, and high cellular density were more frequently observed in carcinogen-treated groups than in carcinogen-nan-treated groups. Histopathologically, as a preneoplastic marker, HAN was maintained only in mammary organ culture of the carcinogen-treated groups. These findings suggest that in vivo trans-formation effects by carcinogens persisted during the mammary organ culture. These results were more characteristic in DMBA than in MNU-treated group. Ducts and terminal ducts appeared to have lost morphology during their growths in case of without diethylstilbestrol (DES). The fact that in vitro organ culture without DES was resulted in abnormal ductular morphogenesis confirms that DES is a physiological regulator of ductular epithelial cell growth.

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Effects of Dietary Peroxidizability Index Values on Hepatic TBARS and Antioxidant Enzyme Activity in 7,12-dimethylbenz[$\alpha$]anthracene-treated Rats

  • Kang Min Jeong;Shin Myoung Suk;Park Tung Nan;Lee Sang Sun
    • Nutritional Sciences
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    • v.9 no.1
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    • pp.14-19
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    • 2006
  • Breast cancer may be the consequence of free radical damage, which is partially caused by the excessive intake of dietary fat and imbalances in antioxidant scavenger system;. In this experiment, we examined! the effects of dietary peroxidizability index (PI) values on hepatic thiobmbituric acid reaction substances (TBARS) and antioxidant enzyme activities in rats treated with 7,12-dimethylbenz[$\alpha$]anthracene (DMBA). Female Sprague-Dawley rats were used and 7,12-DMBA (20 mg/kg body weight) was gastrically intubated at seven weeks of age in order to induce mammary tumors (MT). The levels of dietary PI were 36, 81, 126 and 217 (LPI, MLPI, MHPI and HPI), while dietary polyunsaturated/saturated fatty acids ratio was maintained at the same level (1.0). Fat used in the experiment was mixed with soybean oil, com oil, palm oil, perilla oil, sesame oil, fish oil, and beef tallow. Experimental diets were given for the following 20 weeks. We measured tumor numbers and weights, and then assayed the hepatic TBARS levels and antioxidant enzyme activities such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione-S-transferase (GST) and glutathione reductase (GR). The incidence of Mr was the lowest in the MHPI group. The hepatic TBARS level was significantly raised with increasing dietary PI value. The hepatic SOD and GR activities were differed significantly by dietary PI value. The hepatic SOD activity was negatively correlated with dietary PI value and GR activity was the highest in the rats fed the MHPI diet. When the dietary P/S ratio is kept at 1.0, adequate dietary PI value (PI value of 126) may reduce the incidence and growth of Mr, but this benefit may be lost with higher dietary PI value. These results suggest that the awareness of dietary PI values may help to decrease breast cancer incidence and growth.

Combination between Taxol-Encapsulated Liposomes and Eruca sativa Seed Extract Suppresses Mammary Tumors in Female Rats Induced by 7,12 Dimethylbenz(α)anthracene

  • Shaban, Nadia;Abdel-Rahman, Salah;Haggag, Amany;Awad, Doaa;Bassiouny, Ahmad;Talaat, Iman
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.117-123
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    • 2016
  • Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

Chemopreventive Potential of Annona Muricata L Leaves on Chemically-Induced Skin Papillomagenesis in Mice

  • Hamizah, Sulaiman;Roslida, A.H.;Fezah, O.;Tan, K.L.;Tor, Y.S.;Tan, C.I.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2533-2539
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    • 2012
  • Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

Regulations of Reversal of Senescence by PKC Isozymes in Response to 12-O-Tetradecanoylphorbol-13-Acetate via Nuclear Translocation of pErk1/2

  • Lee, Yun Yeong;Ryu, Min Sook;Kim, Hong Seok;Suganuma, Masami;Song, Kye Yong;Lim, In Kyoung
    • Molecules and Cells
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    • v.39 no.3
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    • pp.266-279
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    • 2016
  • The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

CHEMOPREVENTIVE EFFECTS OF XANTHORRHIZOL

  • Park, Kwang-Kyun;Chung, Won-Yoon;Kim, Hee-Ok;Kim, Hee-Kyong;Park, Min-Ah;Kim, Mi-Jeong;Sohn, Joon-Hyung
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.145-145
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    • 2001
  • Xanthorrhizol is a sesquiterpenoid isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) that has been traditionally used in Indonesia for dietary and medicinal purposes. In our studies to evaluate the cancer chemopreventive potential, xanthorrhizol inhibited the mutagenesis induced by reactive oxygen species in Sa;monella typhimurium TA 102 in a dose-related manner and decreased significantly the incidence and the multiplicity of skin tumors initiated by 7, 12-dimethylbenz[$\alpha$]anthracene and promoted by 12-Ο-tetradecanoylphorbol-13-acetate at 19 weeks.(omitted)

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Effect of Chemical Carcinogens on the Replication, Cytolyticity, DNA Synthesis, and Protein Expression of Herpes Simplex Virus in Viral Infected Cells (발암성 화학물질들이 Herpes Simplex Virus의 복제, 세포융해, DNA 합성 및 단백질 합성에 미치는 효과)

  • Chun, Yeon-Sook
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.213-222
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    • 1992
  • We investigated effects of several chemical carcinogens, i.e., $benzo({\alpha})pyrene$ (BP),7,12-dimethylbenz(a)anthracene (DMBA), nitrosomethyl urea (NMU), and nicotine on the replication, cytolyticity, DNA synthesis, and protein synthesis of type 1 herpes simplex virus (HSV-1) in viral infected Vero cell monolayers. We observed that the BP and DMBA did not show such activity. All chemical carcinogens did not inhibit the synthesis of viral DNA, but the expression of gamma viral proteins that are expressed from the newly synthesized progeny viral DNA was somewhat notably inhibited by BP and DMBA. However, the synthesis of alpha and beta viral proteins was not altered by the chemical carcinogens. These data indicate that the gamma viral proteins expressed from the newly synthesized DNA in the presence of chemical carcinogens in the culture medium may be defective. This is further supported by the fact that the virus fail to replicate in the presence of these chemical carcinogens, in spite of viral DNA and proteins are somewhat normally synthesized.

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Inhibitory Effects of Tualang Honey on Experimental Breast Cancer in Rats: A Preliminary Study

  • Kadir, Erazuliana Abd;Sulaiman, Siti Amrah;Yahya, Nurul Khaiza;Othman, Nor Hayati
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2249-2254
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    • 2013
  • The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (${\leq}2cm^3$) compared to Controls (${\leq}8cm^3$). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.