Τίτλος:
Stage-dependent genetically-based deformities of the regenerating newt
limb from 4-nitroquinoline-N-oxide mutagenesis: Potential embryonic
regulation of cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The effect of the mutagenic carcinogen 4-nitroquinoline-N-oxide (4NQO)
on limb regeneration was studied in adult Triturus cristatus newts.
Delayed limb regeneration was observed when a 10- to 15-mu g crystal of
4NQO was implanted at the late dedifferentiation or late bud stage.
Additionally, 4NQO administration at these stages caused developmental
deformities in skeletal elements of the subsequent regenerates. In
contrast, 4NQO implanted at the wound healing stage did not affect
skeletal morphogenesis. These critical stages of limb regeneration
affected by carcinogen exposure (but not other manipulations) represent
mechanisms distinct from disruption of basement membrane deposition.
Secondary regeneration, initiated by reamputation of the 4NQO-treated
abnormal regenerates 4-5 mm proximal to the site of carcinogen
implantation, produced normal regenerates, setting a limit on the
diffusion distance of 4NQO in the limb. Distal reamputation through
regenerates at the level of the abnormality resulted in regeneration of
the original bone deformity, suggesting that the teratogenic effect of
4NQO is mediated via heritable mutational events in blastema cells.
These results extend a previously published conclusion that 4-NQO is
mutagenic in non-regenerative tissue to include regenerative tissue as
well. However, in spite of mutagenic activity, squamous carcinomas were
not induced by 4NQO exposure at any stage of regeneration. Therefore,
the resistance of regenerative tissue to 4-NQO carcinogenesis is not due
to resistance to mutations, but rather to other mechanisms perhaps
similar to those which regulate malignant cells in murine embryos.
Συγγραφείς:
Zilakos, NP
Zafiratos, CS
Parchment, RE
Περιοδικό:
Differential Equations & Applications
Εκδότης:
Elsevier Sci Ltd, Exeter, United Kingdom
DOI:
10.1046/j.1432-0436.1996.6020067.x
