Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

Abstract

To investigate the modifying effects of eugenol (EUG), a component of cigarette smoke, on lung carcinogenesis, male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 250 mg/kg urethane (UR) or saline, followed by a diet containing 6,000 ppm EUG or basal diet for 26 weeks. Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. In both male and female rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas and carcinomas were observed in all UR-treated groups. However, there were no significant intergroup differences in the incidences and multiplicities of these lesions between the UR alone and UR EUG groups. In non-Tg mice, alveolar/bronchiolar hyperplasias, adenomas or carcinomas were sporadically observed in UR-treated groups of both sexes, with no significant differences in the incidences and multiplicities between the UR alone and UR EUG groups. There were no intergroup differences between them in the PCNA-positive ratios of adenomas or carcinomas and the areas of adenomas or carcinomas to the whole lung area examined. The present results suggest that the EUG treatment does not exert modifying effects on lung carcinogenesis induced by UR in both male and female rasH2 mice and non-Tg mice.

Skeletal Myopathy in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene

“…No abnormalities suggesting muscle weakness or motor function abnormality or abnormal gait were found in rasH2 mice from all of the studies. Bodyweights of rasH2 mice in 26-week studies were about 80-100% of non-Tg mice at 26-weeks, in accordance with the results of the previous reports (14,20,21,28).…”

The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment

“…The anti-carcinogenic effect of eugenol had been investigated in several models [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The anti-carcinogenic effect of eugenol against skin carcinogenesis was investigated by Kaur et al [ 20 ].…”

“…In addition, eugenol reduced the ATP generation and inhibited oxidative phosphorylation and fatty acid oxidation via downregulating of c-Myc/PGC-1β/ERRα signaling pathway and inhibiting ROS production in H-ras transfected MCF 10A breast epithelial cells, indicating that eugenol can prevent breast cancer progression by regulation of cellular energy metabolism [ 27 ]. On the other hand, eugenol treatment does not exert modifying effects on lung carcinogenesis induced by urethane [ 28 ]. No significant differences in the incidences and multiplicities of lung lesions were observed between eugenol and control groups.…”

“…No significant differences in the incidences and multiplicities of lung lesions were observed between eugenol and control groups. In this model of lung carcinogenesis, transgenic mice with the human prototype c-Ha-ras gene received a single intraperitoneal injection of 250 mg/kg urethane, followed by a diet containing 6000 ppm eugenol or basal diet for 26 weeks [ 28 ]. The Table 1 summarize the anti-carcinogenic effect of eugenol.…”