We shall determine whether transformation of 10T1/2 cells produced by various chemical and physical carcinogens can be blocked by ascorbic adic as we have shown is the case for methylcholanthrene-induced transformation. Additional model systems including mouse 3T3, hamster embryo, and mouse epithelial cultures will be examined to see if ascorbic acid can inhibit transformation in each case. The mechanism(s) by which ascorbic inhibits transformation and revents morphologically transformed cells to a normal phenotype will likewise be studied. We shall also examine factors which may be important to the loss of anchorage dependency and gain of tumorigenic potential in morphologically transformed 10T1/2 cells which we have isolated because of their differential response to ascorbate and subsequent capability to grow in semisolid agarose and produce tumors in nude mice. These studies will include possible differences at the cell membrane, cytoskeletal, chromosomal, and DNA levels. Additionally, change at the electron microscopic level will be examined. Finally, it will be determined if ascorbic acid can also prevent carcinogenesis following initiation by a chemical carcinogen in vivo. Wistar rats will be used for the initial studies and if successful we shall extend our studies to guinea pids which, like man, do not synthesize ascorbic acid. These studies should provide not only a better understanding of the mechanism(s) involved in the progression of a transformed cell to a stage where if becomes tumorigenic but also should provide important information in the field of chemoprevention.
| Ibric, L L; Benedict, W F; Peterson, A R (1988) Simultaneous determination of ascorbic acid and dehydroascorbic acid in cultures of C3H/10T1/2 cells. In Vitro Cell Dev Biol 24:669-76 |
