Radiation Enhancement of SV40 Transformation in 3T3 and Human Cells

Pollock, Edward J.; Todaro, George J.

doi:10.1038/219520a0

Cited by 59 publications

(18 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro chemical transforma tion of various rodent cells has been well established (9). Viral transformation has been demonstrated in skin fibroblast cultures derived from normals and individuals with genetic abnormalities including ACR (10)(11)(12)(13)(14). Many attempts have been made to transform various cultured normal or genetically abnormal human cells with chemical carcinogens without success [2,3).…”

Section: Discussionmentioning

confidence: 99%

Heritable Colonic Cancer Syndromes: Induction of Anchorage-Independence in Dermal Cultures Derived from Patients with Adenomatosis of the Colon and Rectum

Bs¹

1980

Oncology

View full text Add to dashboard Cite

After exposure to the mutagen, ethylmethanesulfonate (EMS), or the carcinogen, urethane (UR), anchorage independence was observed in cultures derived from normal skin biopsies from patients with the heritable cancer syndrome, adenomatosis of the colon and rectum (ACR). Such colonies from methylcellulose suspension cultures did not produce tumors in athymic mice. Dissociation of growth in suspension from tumori-genicity was considered to be consistent with the hypothesis that a series of somatic mutation-like events occur in carcinogenesis. Such ACR cells should prove to be useful in studies on the genetic predisposition to cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Heritable Colonic Cancer Syndromes: Induction of Anchorage-Independence in Dermal Cultures Derived from Patients with Adenomatosis of the Colon and Rectum

Bs¹

1980

Oncology

View full text Add to dashboard Cite

show abstract

“…X-irradiation has been shown to promote in vitro transformation in combination with polyoma (4) or simian virus 40 (5,6) in hamster embryonic secondary cultures, hamster cell line BHK 21/13, and 3T3 mouse cell lines. Evidence was presented that the effect in established cell lines was not due to selection of preexisting cells with a greater susceptibility to transformation.…”

mentioning

confidence: 99%

X-Irradiation Enhancement of Transformation by Benzo(a)Pyrene in Hamster Embryo Cells

DrPaolo

Donovan

Nelson

1971

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The addition of benzo(a)pyrene to cells obtained from Syrian hamster embryo cultures that had been plated to produce discrete colonies resulted in transformation. Altered colonies were not seen in controls. Prior irradiation of hamster embryo cells increased the transformation by benzo(a)pyrene, both per cell and per total colony. Maximum enhancement occurred when benzo(a)pyrene was added 48 hr after irradiation. Enhancement was greatest after 250-500 R, and decreased with higher doses of radiation. Although the link between radiation (both x-and UVirradiation) and cancer has been recognized since the discoveries of x-rays and natural radioactivity, the use of physical agents as carcinogens or cocarcinogens for in vitro studies has been extremely limited. X-irradiation has been shown to promote in vitro transformation in combination with polyoma (4) or simian virus 40 (5, 6) in hamster embryonic secondary cultures, hamster cell line BHK 21/13, and 3T3 mouse cell lines. Evidence was presented that the effect in established cell lines was not due to selection of preexisting cells with a greater susceptibility to transformation. Cell transformation in vitro by x-irradiation only has been reported in primary cell lines of hamster embryo cells (7), but has not been observed in the irradiated controls of the experiments involving radiation and viruses or after repeated weekly irradiation of a hypotetraploid fibroblast line derived from mouse spleen (8).Abbreviation: BP, benzo(a)pyrene. MATERIALS AND METHODSThe tissue-culture fluids and medium as well as the feeder layer cultures, the source and culture of cells from minced hamster embryos, and the standard conditions for the transformation assay have been described in detail (2). Cells derived from whole rat or hamster fetuses were grown as monolayers in Dulbecco's modification of Eagle's medium (MEM) with either 10% calf serum or 10% fetal bovine serum. In all experiments 2-to 4-day-old secondary or tertiary hamster cultures obtained by seeding 5 X 106 cells/100 ml plastic dish were used. Feeder layers composed of secondary cultures of rat embryo cells were irradiated as confluent monolayer cultures in 2 ml of medium. A Picker Portable Industrial x-ray apparatus (T55-433) was used at 110 kV and 5 mA, 2225 R/min, adjusted so that a total of 5000 R in air was delivered to a distance of 22.2 cm. Hamster cells were irradiated as confluent monolayers in 100-mm plastic Petri dishes with a Westinghouse Quandrocondex machine with two tubes, above and below, with the following factors: 200 kV (CP), 0.25 Cu + 0.55 mm Al filtration in each tube (HVL 0.9 mm Cu), 15 mA, 54 cm TSD, output 139 R/min. After being irradiated with 150-1000 R, the cells were plated on irradiated rat fibroblast feeder layers in 60-mm Petri dishes. Each value represents data obtained from at least 12 plates. Because unirradiated and irradiated cells had different survival rates, it was necessary to vary the number of hamster cells seeded to obtain the same approximate number of colonies. At desig...

show abstract

“…Additionally, we re- cently reported that thymidine analogs and aging of primary cells in vitro rendered the cells increasingly sensitive to SV40 transformation (9). Physical damage to the DNA of the irradiated cells ( l l ) , recycling the cells to a partcular mitotic phase postirradiation, or induced DNA synthesis (8) or repair (9) may be responsible for the observed enhancement in vitro.…”

Section: Materials Andmentioning

confidence: 99%

“…Exposure of mouse fibroblasts to radiomimetic thymidine analogs enhanced the efficiency of SV40 transformation 5-fold (5)(6)(7). X-irradiation of the 3T3-mouse cell line markedly sensitized the cells to transformation after infection with SV40 (8). Hamster embryo cells in primary tissue culture were rendered 50-fold more susceptible to SV40 transformation when treated with 150 R 'of X-irradiation prior to infection than were nonirradiated cells (9).…”

mentioning

confidence: 98%

Radiation-Enhanced Oncogenesis by SV40

Coggin

Harwood

Anderson

1970

Experimental Biology and Medicine

View full text Add to dashboard Cite

The induction of primary virus tumors in hamsters by SV40 after an extended period of time after neonatal infection is well documented (1-3). For experimental studies it would be of considerable advantage if the incubation period could be reproducibly shortened. Stoker (4) observed that the frequency of in vitro cellular transformation produced by polyoma virus was increased among BHK-21 hamster cells that survived Xirradiation pretreatment. Exposure of mouse fibroblasts to radiomimetic thymidine analogs enhanced the efficiency of SV40 transformation 5-fold (5-7). X-irradiation of the 3T3-mouse cell line markedly sensitized the cells to transformation after infection with SV40 (8). Hamster embryo cells in primary tissue culture were rendered 50-fold more susceptible to SV40 transformation when treated with 150 R 'of X-irradiation prior to infection than were nonirradiated cells (9). In this study we have asked whether enhancement of virus tumorigenesis occurs in vivo, which is similar to that observed in vitro after X-ray pretreatment of the SV40 infection site in neonatal hamsters.Materials and Methods. Virus. Simian virus 40, strain VA45-54 was prepared in green monkey kidney cells (GMK) and contained lo9 plaque-forming units per ml of virus when assayed in GMK. Full-strength virus and virus diluted 1 : 1 in Hanks' balanced salt AT (40-1 ) 3 646.solution were tested. Newborn Syrian golden hamsters were positiloned beneath a lead shield disc with tape so that the right scapular region or the left lower flank was exposed tangentially to a 5-mm opening.Radiation. X-ray from a Maxitron "300" source equipped with 0.5 mm aluminum and 0.42 copper filters was delivered to the center of the disc from a distance of 2 2 cm. Tissue regions in the openings were 5 cm from target center and were exposed to 150 R of X-irradiation.Infection. SV40 virus (0.2 ml) was inoculated subcutaneously directly intlo the irradiated target region immediately after X-ray exposure, and neonates were returned to their mothers and palpated weekly for tumors. Animals were weaned 21 days after birth. Controls included radiation treatment alone, virus infection alone, radiation exposure, and injectiton of passage fluid control solution containing no virus or radiation exposure at one site and virus injections at another.Results. Results presented in Fig. 1 show that infection with undiluted virus produced tumors in nonirradiated hamsters beginning after 130 days postinfection, and 80% of the animals developed subscapular tumors by 160 days. However, tumors appeared more than 50 days earlier in hamsters receiving X-ray in the subscapular region prior to neonatal infection, and 88% of the animals had tumors in this group by day 160. Similar results were observed when X-ray exposure and virus were given in the left flank area with the exception that all animals developed tumors.Using diluted virus suspensions (Fig. 2) in nonirradiated animals no difference could be detected in the time of appearance of the first tumor (130 days) when infected with 1109

show abstract

Radiation Enhancement of SV40 Transformation in 3T3 and Human Cells

Cited by 59 publications

References 10 publications

Heritable Colonic Cancer Syndromes: Induction of Anchorage-Independence in Dermal Cultures Derived from Patients with Adenomatosis of the Colon and Rectum

Heritable Colonic Cancer Syndromes: Induction of Anchorage-Independence in Dermal Cultures Derived from Patients with Adenomatosis of the Colon and Rectum

X-Irradiation Enhancement of Transformation by Benzo(a)Pyrene in Hamster Embryo Cells

Radiation-Enhanced Oncogenesis by SV40

Contact Info

Product

Resources

About