Modifying the tumor effects in the lungs of laboratory mice with lichen extracts

The anti-tumor properties of common lichens of Belarus: Hypogymnia physodes, Ramalina pollinaria, Cladonia arbuscula, Evernia prunastri were studied using the models of spontaneous and induced carcinogenesis in mice Af lungs. Without exposing to a carcinogen in 20 weeks after taking aqueous lichen extracts (1 g/l) of 4 species for 28 days, only C. arbuscula showed the pro-carcinogenic properties almost doubling the average number of pulmonary adenomas per mouse. R. pollinaria and E. prunastri did not provoke spontaneous carcinogenesis and had a corrective effect significantly reducing the number of adenomas per mouse by 21 and 45 %, respectively. To carry out induced carcinogenesis, after 2 weeks of taking aqueous extracts, mice were injected intraperitoneally with urethane (1 g/kg). The analysis of the total number of adenomas per mouse showed a pro-tumor tendency for C. arbuscula, and the analysis of the number of adenomas of 1 mm and more showed that for H. physodes. The extracts do not affect the proportion of urethane adenomas of various sizes in their total number, but increase the incidence of high-yield adenomas of various sizes; at the same time, H. physodes has a much greater pro-carcinogenic activity according to the incidence of high-yield adenomas of 1 mm or more. The analysis of the total number of urethane adenomas per mouse, as well as adenomas of 1 mm showed an anti-tumor tendency for R. pollinaria and a pro-tumor tendency for E. prunastri. Taking E. prunastri increased the incidence of high-yield adenomas of various sizes, along with a notable increase in the incidence of low-yield adenomas. In the case of R. pollinaria, the increase in the incidence of low-yield adenomas was supplemented by a sharp decrease in the incidence of high-yield adenomas. As a result of the experiment, E. prunastri has exhibited both the pro-carcinogenic activity and the anti-tumor properties, but R. pollinaria has revealed a pronounced anti-tumor potential.

Deficiency in Poly(ADP-ribose) Polymerase-1 (PARP-1) Accelerates Aging and Spontaneous Carcinogenesis in Mice

Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosyl)ation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosyl)ation and PARP-1 may also play an important role in aging. Here we show that PARP- mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP- mice. The incidence of spontaneous tumors in both PARP- and PARP- groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP- mice than PARP- mice (72% and 49%, resp.; .05). In addition, spontaneous tumors appear earlier in PARP- mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.