Awardee OrganizationMASSACHUSETTS INSTITUTE OF TECHNOLOGY
Description
Abstract Text
We have discovered that when our human cell line, AHH-1, which expresses
cytochrome P-450 1A1, is exposed continuously to low concentrations of
potent airborne mutagens such as benzo(a)pyrene and naphtho(a)pyrene that
they switch from a high mutation rate to a low mutation rate after 5 days.
This low mutations rate is only some three fold higher than seen for
spontaneous mutation in the concurrent untreated controls. Studies with
radioactive benzo(a)pyrene show that the rate of DNA adduct formation is
unchanged by this phenomenon. The ratio of the rate of mutation relative
to the rate of constant DNA adduction is changed by a factor of four
suggesting induction of a post-DNA adduction process such as DNA repair is
occurring.
Because such a phenomenon would, if occurring in vivo, represent a major
physiologic response protecting against induction of mutations by airborne
toxicants. Our studies so far establish that the induction of the
mutation-resistance by benzo(a)pyrene confers cross-resistance to mutation
by the potent airborne mutagen, cyclopenta[c,d]pyrene. Secondly, we have
found that another potent airborne mutagen naphtho(a)pyrene induces
resistance to mutation in a time dependent pattern similar to that of
benzo(a)pyrene. Finally, we have found human cell lines derived from AHH-1
which are markedly sensitive to mutation by air sample extract under short
term high dose conditions giving use a useful mode for proposed long term
dose mimicking conditions of samples, source samples and their extracts
and subfractions on these human cells under these long term low dose
conditions which more closely approximate the conditions of exposure in
the human bronciolar tree, (b) discover it the "mutation resistant state"
is induced by exposure to raw air particulates, by particulate extracts
and by particulate extract subfractions, and (c.) carry out appropriate
studies of the process at the cellular and molecular levels.
National Institute of Environmental Health Sciences
CFDA Code
DUNS Number
001425594
UEI
E2NYLCDML6V1
Project Start Date
03-August-2000
Project End Date
31-July-2003
Budget Start Date
01-October-1998
Budget End Date
30-September-1999
Project Funding Information for 2000
Total Funding
$222,065
Direct Costs
$222,065
Indirect Costs
Year
Funding IC
FY Total Cost by IC
2000
National Institute of Environmental Health Sciences
$222,065
Year
Funding IC
FY Total Cost by IC
Sub Projects
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