The effects of Fhit on tumorigenesis after multi-exposure to low-dose radiation

Abstract

Low-dose (</= 0.1 Gy) radiation could reduce high-dose induced damage including tumorigenesis. However, it remains unclear whether multi-exposure to low-dose radiation at a high dose rate has any risk for increasing tumorigenesis, and whether Fhit plays any role in the process. The purpose of this study is to investigate the effects of multi-exposure to low-dose radiation at a high dose rate on tumorigenesis, and the role of Fhit in it. We irradiated Fhit(+/+) and Fhit(-/-) mice with 1 Gy/1 or 0.1 Gy x 10 exposures at a dose rate of 1 Gy/min, sacrificed the mice at 1.5 years after radiation and observed multi-organ tumorigenesis. The results showed that although the spontaneous tumorigenesis in these mice was relatively high, 1 Gy/1-exposure dramatically increased the tumorigenesis including lung and liver tumor. Fhit(-/-) mice showed more tumorigenesis than Fhit(+/+) mice after 1 Gy/1-exposure. However, 0.1 Gy x 10 exposures did not increase tumorigenesis, and there was no statistical difference in tumorigenesis between Fhit(+/+) mice and Fhit(-/-) mice following 0.1 Gy x 10 exposures. Our results suggest that 0.1 Gy, even after multiple exposures, does not increase tumorigenesis, and Fhit could prevent high-dose radiation-induced tumors but has no effect in a low-dose environment.

Keywords: Fhit; ionizing radiation; low dose; tumorigenesis.

Figure 1

Different type tumors were observed in the mice. The mice were sacrificed as described in Materials and Methods. The multi-organs including lung, liver, kidney, intestine and multi-glands including ovary, testis, parotid and sublingual gland were taken for histological slide preparation. The samples were fixed in buffered formalin and sent to the University' pathology facility for tissue slicing and hematoxylin & eosin (H&E) staining. The magnification is 100 X.

Figure 2

Grade of the size in liver or lung tumors. The size of liver or lung tumors was graded as: – (no tumor), + (tumor size < 0.1 mm), ++ (tumor size is between 0.1-0.5 mm), +++ (tumor size is between 0.5-1mm), and ++++ (tumor size > 1 mm). The indexes were calculated by combining the diameters of all liver or lung tumors in each mouse. The magnification is 100 X.