Modulatory effects of Azadirachta indica leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice.

The modulation in biochemical status of skin and hepatic tissue at the time point of commencement of promotion stage of skin carcinogenesis in mice and its intervention with aqueous Azadirachta indica leaf extract (AAILE) were investigated. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for 2 weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for 6 weeks on the depilated skin of mice and AAILE was administered orally at a dose level of 300 mg/kg body wt thrice a week for 10 weeks. DMBA/TPA treatment upregulated the phase I enzymes in skin and hepatic tissue, as revealed by the increased cytochrome P450 (CYP) and cytochrome b5 (cyt b5) levels and aryl hydrocarbon hydroxylase (AHH) activity when compared to the control group and differentially modulated the activities of phase II enzymes like glutathione-s-transferase (GST), DT-diaphorase (DTD) and uridine diphosphate glucuronosyltransferase (UDP-GT). AAILE treatment decreased the DMBA/TPA-induced increase in cutaneous CYP level and enhanced the DTD and UDP-GT activities when compared with DMBA/TPA group. In the hepatic tissue of AAILE + DMBA/TPA group, an increase in UDP-GT activity was observed when compared to DMBA/TPA group. DMBA/TPA treatment did not alter the skin lipid peroxidation (LPO) level when compared to control group, however, in the animals that received AAILE treatment along with DMBA/TPA, a significant increase in LPO was observed when compared to control group. This was associated with a decrease in cutaneous reduced glutathione (GSH) level of AAILE + DMBA/TPA group. Enhanced LPO level was observed in the hepatic tissue of DMBA/TPA and AAILE + DMBA/TPA groups when compared to control group. However, no alteration was observed in their hepatic GSH levels. The micronuclei score in hepatic tissue did not exhibit significant inter-group differences. The results of the present study suggest that apart from skin, liver may be affected during DMBA/TPA-induced skin tumorigenesis. AAILE treatment has the ability to modulate these changes potentially influencing the process of tumor formation. These findings seem to be important to carcinogenesis and its intervention with anti-cancer agents.

Análise do potencial carcinogênico de dentifrício com peróxido de hidrogênio e de agente clareador dentário: avaliaçöes clínico-macroscópica e microscópica em hamsters no modelo de carcinogênese bucal DMBA-induzida / Analysis of carcinogenic potential of toothpaste with hydrogen peroxide and dental bleaching agent: microscopical and clinical-macroscopical evaluation in hamsters in the DMBA-induced oral carcinogenesis model

Estudou-se de forma comparativa, os efeitos de peróxido de hidrogênio sobre a mucosa bucal de hamsters. Utilizou-se 96 animais, divididos em 8 grupos, aplicando-se: água destilada; DMBA; peróxido de carbamida a 10 por cento com carbopol; peróxido de hidrogênio a 27 por cento; dentifrício com peróxido de hidrogênio; DMBA+peróxido de carbamida a 10 por cento com carbopol; DMBA+peróxido de hidrogênio a vinte e sete por cento; DMBA+dentifrício com peróxido de hidrogênio. Pode-se constatar que o peróxido de hidrogênio, nas várias formas aplicadas, näo induziu alteraçöes epiteliais de nenhuma natureza e morfologicamente detectáveis à microscopia óptica de luz. Os mesmos produtos, aplicados após o DMBA, aumentaram o número de animais mais severamente comprometidos e promoveram lesöes carcinomatosas mais amplas e severas na mucosa, quer seja do ponto de vista macro ou microscópico. Concluiu-se que o peróxido de hidrogênio atua como agente promotor da carcinogênese, pois potencializa o efeito de agentes iniciadores na carcinogênese bucal química

Study models for inducing tumors by 7, 12-dimethylbenz(A): antracene in rat mammary gland

Cinco modelos de estudo (A,B,C,D,E) foram usados para investigar o efeito do 7,12-dimetilbenz(a)antraceno em induzir tumores no tecido mamário de ratas Sprague-Dawley. Cada grupo foi submetido ad libitum às seguintes dietas: grupo A - raçäo comercial ; grupos B e C - uma dieta semipurificada rica em ácido linóico; grupo D - uma dieta semipurificada rica em ácido graxo saturado; grupo E - uma dieta gordurosa de 50 porcento de óleo de soja (rico em ácido graxo essencial), 25 porcento de óleo de oliva (rico em ácido oleico) e 25 porcento de óleo de coco (rico em ácido graxo saturado). Os grupos A,B,C,D e E desenvolveram 52 porcento, 76 porcento, 88 porcento, 60 porcento e 67 porcento de tumores, respectivamente. Nos grupos testes A,B,C,D e E, o primeiro tumor palpável foi visto 200 a 52, 103 a 36, 48 a 1, 133 a 62 e 183 a 45 dias após a administraçäo do DMBA, respectivamente. 14,8 porcento, 97,5 porcento e 41,7 porcento de todos os tumores foram classificados como adenocarcinomas. Os resultados sugerem que o modelo de estudo C foi o mais efetivo, induzindo, o maior, incidência de adenocarcinomas nos ratos tratados por DMBA, os sintomas foram evidentes no menor tempo experimental.

Effect of 9,10-dimethyl-1,2-benzanthracene on the growth of hamster dermal fibroblasts in primary culture.

Newborn Syrian hamster dermal fibroblasts in primary culture have high plating efficiency, manifest as homogeneous contact-sensitive monolayer in mass cultures and above all possesses a short life-span of 15-20 days in culture. These cells are quite sensitive to mutagenic carcinogens. The DMBA treatment induced multi-layer and foci formation and growth in soft-agar suggesting that immortal variants can be obtained by treatment with carcinogens.