Modulation of expression of virus-like elements following exposure of mice to high- and low-LET radiations

Abstract

Modulation of virus expression has been reported following exposure to a variety of cellular stresses, including UV radiation and heat-shock. The experiments reported here were designed to examine expression of endogenous VL30 (virus-like 30 S) elements following exposure of whole mice to ionizing radiations. Whole mice were exposed to doses of neutrons (50 cGy) or gamma-rays (300 cGy) shown to be equally efficient in cancer production in the whole animal, and tissues were harvested at 10 and 60 min following completion of the exposure. RNA extracted from these tissues and from tissues of untreated controls was examined for VL30 RNA accumulation by dilution dot blot and Northern blot analyses. These studies revealed that neutrons repressed VL30 RNA accumulation evident within 10 min following exposure in brain, gut, thymus and spleen but not in liver, in which VL30 RNA was unaffected by radiation exposure. During this same time interval, gamma-rays induced VL30 expression in gut and brain and to a lesser extent in liver. These experiments suggest the presence of a differential molecular response following whole-body exposure to high- versus low-LET radiations. In addition, this work demonstrates that ionizing radiations may affect expression of murine endogenous viral sequences.

Osteosarcomagenic doses of radium (224Ra) and infectious endogenous retroviruses enhance proliferation and osteogenic differentiation of skeletal tissue differentiating in vitro

“…Molecular data supporting this notion were derived from radium-and thorium-induced osteosarcomas showing new retroviral integrations in the DNA of the tumor cells but not in normal bone marrow cells of tumor-bearing mice [37], amplification and enhanced expression of the myc oncogene [40], mutations and rearrangements together with enhanced expression of the p53 tumor suppressor gene [39], and disruption of wt p53 gene function by retroviral insertion (Mitreiter et al, manuscript submitted). Similar observations were derived from y-irradiated cells, including the induction of endogenous retroviral sequences in tissues from irradiated mice [22] and cell lines [13] and induction of oncogenes [26], notably the fos oncogene [43], which in addition to its function as a member of the AP-I transcription factor complex has recently been shown to increase genomic instability [44]. These data suggest that proliferation-as well as differentiation-associated cellular genes represent critical targets for ionizing irradiation.…”

Unusual long target duplication by insertion of intracisternal A‐particle element in radiation‐induced acute myeloid leukemia cells in mouse

“…Gene rearrangement is still not well understood at the molecular level in radiation-induced tumor cells. However, speculative data were presented that X-irradiation increased in the level of message for VL30-retro element which is also a member of the mouse retrotransposon family [26]. If IAP message is increased with VL30 mRNA, then frequency of incorporation can be increased.…”

Mechanisms of radiation-induced gene responses

“…many studies have identified genes induced in response to DNA-damaging agents such as UV and ionizing radiation (Anderson and Woloschak 1992;Boothman et al 1991;Fornace et al 1988Fornace et al , 1989Fornace, 1992;Herrlich et al 1992;Hallahan et al 1989;Libertin et al 1994;Martin et al 1993;Munson and Woloschak 1990;Panozzo et al 1991;Peak et al 1991;Ramsamooj et al 1992;Ronai et al 1988;Stein et al 1989a, b;Valerie et al 1988;, 1992Woloschak et al 1990aWoloschak et al , b, c, 1994Woloschak et al , 1995aSakakeeny et al 1994). The collective contribution of these studies has led to the implication of several different transcription or regulatory elements as playing a key role in the immediate early response, including p53, AP-1, NF-~€3, and others (Hallahan et al 1991;Kastan et al 1991;Nelson and Kastan 1994;Sun et al 1995;Brach et al 1991;Angel et al 1987;Andahbi et al 1993;Kharbanda et al 1995;D a m et al 1992Mohan and Meltz 1994: Prasad et al 1994: Sahijdak et al 1994McKenna et al 1991), and the identification of nuclear and nonnuclear events as playing essential roles in the actual induction process (Stein et al 1989a, b;Uckun et al 1992Uckun et al , 1993Simon et al 1994;…”