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Tentative Proposals A Lc.

Cytogenetic effects of radiations on bacteria
Departuent of Genetice; University of Wisconsin; “adison, ‘ia.
Joshua Lederberg (Associate Professor of Genetics)

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Support 4e request’ from the Atomic Energy Commission for tho

preliminary exploration of e subject which may throw fundsrenteal light

on the mecheniem of biological ection of ionizing radiations. The material

to be studied is diploid celle of Escherichia coli. York in progress has
shown that this material can be used to test the sighhficance of recessive
lethal mitations in the bactericidal effects of chemical mitagens euch

as nitrogen mustard or physical agents such as ultra-violet light. In

diploid cells, lethal mutations can be detected owing to their temrorery
masking by the unmutated genome: in haploid celle, of course, lethal mutations
result in cell death, and are thus not amenable to study.

Work in progress Indicatee that, contrary to expectetion, lethal
mutations play an insignificant role in bacterial killing by nitrogen mustard
or ultraviolet light. Bactericide by these, and a large number of other
agents, including hydrogen veroxide, formaldehyde, ard X-rays (in a single
preliminary experiment) ia,however.accompanied by complex genetic reorrani zations,
not completely understood as yet, but including the production of cells with
haploid, rather than diploid constitution. It 18 also avnarent that these
chenres are accompanied by disturbances in the division and distribution of
the nuclear bodies in the treated bacteria.

The present project concerns the extension of this genetic and cyto—
logical work with special reference to the effects of X-raye (and subsequently,
of other fonizing radiations). Because the project is already under way to
some extent, with respect to chemical and ultra-violet effects, a mdest re-

quest 4s made for the first year, as the maior aim of the project during this
interval ia detwemine the advisability of 2 concerted attack upon this
problem. It is anticipated that inoreased working space for research
will he available to the investicator in 1952, 1? an expansion of the
program in the areas of intorest to tho Atomic Energy Cormiscion appears
desirable, both to the Gomdssion and ths investigator.

in this interval of axploration, ho new personae? will be required.
The genetic work will be corvtimed by the investizstor, with tio ansistance,
particularly in cytological appeets, of graduste student recearc’. asslotants
already in residence. Financial support will be required prinerily for
the purchase of roantgen-dosimetric equinment needed for kinetic ctudies
on the comparative rates of sterilization of dinloid ani heoloid cells, and

for additional suoplics incidental to the sroject.

although none of theee ic prigarily suited to blolesical research. “iowever,
for the prosent., the purehase of 1 now machine for tie currant crojest does
nat scom to be Justified, and it is hoped that the mreaent faicitiies will
be adogunte. A radioactive Co source will b: avAdlable someoomteae arcteat
in another research erowm, ami tre inetallation of s betsatron 1+ antictoated.
Basic anvaratua and Pactlities for bacteriological reacarch tieve alretly
been established.

Budget. For roentgen-dosimetric equinment, and other

aoparetus and supplies 4500.90

Overhead...e (at established rate)

Tota | *500.00 plus
overhead.

ho projesed term for the preltainery project is Mare) 1, 1901 to
February 2, 1952. Mowever, 4£ ressarai results or olhor factor? intervene
whioh make further action advisable, the investigator may apply for subsidiary
suppert prior to the expiration of this term. The probable term of an extended

project would be about four years, unless full-time employees displace
our graduate students.

The principal investigator is in charge of allaboratory devoted to
wicrobicl cenetie research, and nouring, at present, throe pro/uate
resoaroh acsietants and one postdootoral rescaroh associate. Min tosching
duties, aside from thosa incidental to the leborntor;y, cre aininal. A number
of research projects are underway in the laborator;, dosling crinartl+y with

formal and rhysiological
a; Remmucbertins cenctice of

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Grohbortchte coli; b) heet-varesite relationships
in lysesentc bacteria; c) eereenine fer cenotic recombination in talmnella
and other bacteria: d) cytological carmparisons of ha lhid and dtvloid T. cold,
amd] the effect of bactericides, and ae) nechanian of antion of bactericidal
agentyoe

The laboratory's program recofves support fror. other federal are nctes
as follows?

For 1951-52: National Inetitutes of Nealth 4 4,320
(Genetics of Salmoneilad

Chemivual Corps 6,006 (15 moe.)
Lysogenic Bacteris.)
Requerts anticipated for 1951-52

National Inetiteu&en of Heelth Py O0C.
(Genetics of Rreteria)

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