Alfred Knudson: Two Hits Times 25 Years | JNCI: Journal …
The Knudson two-hit model explains the tremendously high prevalence ofcertain tumors in peopleunfortunate enough to have inherited one defective copy of atumor suppressor gene.
proposed his famous “two-hit” hypothesis of tumor ..
Our lab subsequently used the Knudson two-hit hypothesis of tumorigenesis to provide the first evidence that the also functions as a tumor suppressor (). Since IGF2R is imprinted (i.e. one copy of the gene silenced by DNA methylation), this finding thrusted me into the rapidly growing research field of . Interestingly, I had the honor of finally meeting Dr. Knudson almost a decade later in Stockholm, Sweden at the 2004 Nobel Symposium on epigenetics entitled, . I will greatly miss these pioneering scientists upon whose shoulders I stood.
Another group of effect parameters relate to genotoxic effects (changes in the structure of chromosomes). Such effects may be detected by microscopy of white blood cells that undergo cell division. Serious damage to the chromosomeschromosomal aberrations or formation of micronucleican be seen in a microscope. Damage may also be revealed by adding a dye to the cells during cell division. Exposure to a genotoxic agent can then be visualized as an increased exchange of the dye between the two chromatids of each chromosome (sister chromatid exchange). Chromosomal aberrations are related to an increased risk of developing cancer, but the significance of an increased rate of sister chromatid exchange is less clear.