integrity is maintained until the final stages of apoptosis, when the membrane blebs and pinches off to form
apoptotic bodies. Cleavage of nuclear DNA at linker regions between nucleosomes is carried out by a
DNAase, which is activated by caspases. Cells, such as lymphocytes and serous acinar cells that have a pro-
apoptotic tendency, are generally radiosensitive, not radioresistant. In irradiated tissues, apoptotic cells
often appear singly and in isolation.
7. A The majority of both normal and tumor cells die by mitotic catastrophe following one, or no more than a
few, abortive mitotic cycles. However, until these cells attempt their first division post-irradiation, there is
no morphological evidence of injury. In comparison to cells undergoing apoptosis, those undergoing necrosis
demonstrate a loss of membrane integrity, a swelling of the cytoplasm and mitochondria, and random
degradation of DNA (leading to a smear following agarose gel electrophoresis). An alternate pathway by
which cells cease to proliferate following lethal doses of radiation is permanent growth arrest (also called
replicative senescence); cells acquire a senescent-like morphology, characterized by increased granularity
within the nucleus, accompanied by increased levels of p16
INK4A
(Cdkn2a) and SA--galactasidase. A number
of pathways can be activated that lead to apoptosis, only some of which are p53-dependent.
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8. C Cells undergoing apoptosis exhibit nuclear fragmentation. Apoptosis does not induce an inflammatory
response, unlike necrosis. Apoptotic cells do not exhibit an increased expression of the MSH2 gene, whose
product is involved in mismatch repair. Apoptotic cells do not swell, but exhibit condensation and fragment
into apoptotic bodies. Apoptosis can take place during interphase.
9. C The extrinsic apoptotic pathway involves stimulation of TNFR family members. Caspase 8 is an important
initiator caspase for the extrinsic mechanism. p53 upregulates apoptosis. BAD is a pro-apoptotic protein.
Leakage of cytochrome c from the mitochondrial membrane is a central aspect of the intrinsic apoptotic
pathway.
10. A Bcl-xL prevents apoptosis primarily through inhibition of cytochrome c release
from the mitochondria.
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11. A The concept of synthetic lethality has gained significant attention in adult oncology in recent years. Two
genes or pathways are considered to be synthetically lethal if inactivation of either does not kill cells, while
simultaneous inactivation of both is lethal. Thus, if a tumor harbors a mutation in one gene of a “synthetic
lethal pair”, targeting the corresponding gene in the pair will selectively kill cancer cells while sparing normal
cells without the cancerous mutation. This concept has also been extended to include oncogenic mutations
and unique translocations. One of the most well-known examples of synthetic lethality is the interaction