LWBK1006-07 LWW-Govindan-Review November 22, 2011 13:54
90 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology ReviewANSWERS
Answer 7.1. The answer is A.
There are two generally accepted mechanisms of repair. They are broadly
known as the HR or NHEJ. HR functions by replicating the missing
genetic information from the homologous DNA template. NHEJ func-
tions by degrading the single strand at each side of the break and then
annealing the two ends in a region of microhomology. The NHEJ may
result in loss or gain in genetic information and is mutation prone. Some
have suggested that HR and NHEJ have overlapping complementary
roles. NHEJ is a dominant mechanism for repairing double-stranded
DNA breaks in mammalian cells. Several investigators have demonstrated
enhanced radiosensitivity of human cell lines by inhibiting the proteins
required for NHEJ.Answer 7.2. The answer is D.
All other statements are true. The indirect effects of x-rays predominate
the biologic effects seen with x-rays. The photons cause ejection of fast
electrons. The ejected fast electrons can directly damage the DNA (direct
action) or, more commonly, the fast electrons interact with plentiful water
molecules to produce hydroxyl radicals (OH—), which in turn can dam-
age the biologic target (indirect action).Answer 7.3. The answer is C.
Although single-stranded and double-stranded breaks are observed from
ionizing radiation, it is the double-stranded breaks that are thought to
represent the lethal event. Although the majority of the radiation-induced,
double-stranded breaks are rejoined in cells within 2 hours after exposure,
the process can continue for 24 hours. In mammalian cells, choice of
repair is biased by phase of cell cycle and by abundance of repetitive
DNA. HRR is used primarily in late S to G 2 phase of cell cycle, and
NHEJ predominates in the G 1 phase of cell cycle. However, this is not
an absolute, and factors in addition to cell cycle phase are important in
determining which mechanism will be used to repair DNA strand breaks.
NHEJ while effective is known to be highly error prone.Answer 7.4. The answer is B.
D 0 is related to the slope of the exponential survival curve and represents a
dose that is required to reduce the surviving fraction to 0.37% or 37% of
the original population. The smaller D 0 represents more radiosensitivity.
Mammalian cell lines display a “shoulder” in the low-dose region and
the exponential relation at higher doses. The “shoulder” represents a
reduced efficiency of cell killing. The linear quadratic model rather than
the linear model best describes the cellular response to radiation. The
postirradiation conditions that suppress the cell division are the ones most
favorable to potentially lethal damage repair.