Appropriate balance between proliferation and apoptosis is critical for mammary gland development and is often altered during tumorigenesis. Carcinogens like radiation induce DNA damage and activate protective responses such as cell cycle arrest and apoptosis. We used @entity19 carrying @entity53618 (-/-) and/or @entity899 (-/-) mutations to evaluate the individual and combined effects of these genes on cell proliferation and apoptosis in the developing mammary gland. @entity19 were exposed to 5Gy of radiation or chamber exposure (controls) followed by injection with @entity1603 . Mammary glands were collected 6 h post-radiation exposure and evaluated for proliferation (BrdU) and apoptosis (TUNEL) in @entity454 ( @entity454 ) and ducts. Under control conditions, the @entity53618 mutation reduced proliferation and apoptosis in @entity454 but not ducts, whereas the @entity899 mutation reduced apoptosis in @entity454 and ducts but did not influence proliferation. Despite these alterations in proliferation and/or apoptosis, neither mutation, either individually or combined, significantly altered the overall balance between the two as measured by the proliferation to apoptosis ratio (growth index). Following irradiation, the @entity53618 mutation had no significant effect on proliferation or apoptosis, whereas the @entity899 mutation resulted in reduced apoptosis in @entity454 and ducts but did not significantly influence proliferation. Neither mutation by itself altered the growth index in the @entity454 after irradiation although combined @entity53618 / @entity899 mutation caused significantly increased proliferation, reduced apoptosis, and an elevated growth index in @entity454 and ducts. These results reveal both independent and collaborative growth regulatory roles for @entity53618 and @entity899 under normal and adverse environmental conditions. Additionally, we demonstrate the importance of gene-environment interactions by showing that @entity53618 - and @entity899 -deficient @entity19 can compensate for their @entity74 under control conditions but not after exposure to radiation. We also demonstrate distinct spatial differences in the cellular functions of @entity53618 and @entity899 and show that combined mutation of both genes is more detrimental than loss of either gene alone.

Mutant @entity53618 / @entity899 XXXX exhibit altered radiation responses in the developing mammary gland.

@entity1603 :: ('MESH:D001973', 'Chemical') :: ['BrdU'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity899 :: ('22060(Tax:10090)', 'Gene') :: ['p53'] @entity53618 :: ('12190(Tax:10090)', 'Gene') :: ['Brca2'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic deficiencies'] @entity454 :: ('MESH:D007676', 'Disease') :: ['terminal end buds', 'TEB']
@entity19 :: (10090,Species) :: ['mice']
