Re: Male Preconception Risks

["Otto G. Raabe" <ograabe@ucdavis.edu>]

At 05:05 PM 7/28/00 -0500, Chris Alston wrote:
>>
>>Can somebody provide information concerning the risks and safeguards
>regarding male exposures prior to conception.  I am specifically interested
>in the low therapy exposure range (5 mCi I-131) and the amount of time to
>recommend (if any) to abstain from reproductive activities.  Your
>assistance in this matter would be appreciated.
>************************************************************************
July 31, 2000
Davis, CA

The following abstract from the 1997 HPS meeting and the appended
references would suggest that Type A/B spermatogonia are the most sensitive
germ cells for preconception radiation effects. In men, these are present
about 8 weeks before the mature sperm. Hence, conception should be delayed
at least 12 weeks after acute irradiation of the reproductive organs to
avoid the potential heritable effects.

Otto
***********************************************
HEALTH PHYSICS IMPLICATIONS OF STUDIES OF BRIEF IRRADIATION OF
REPRODUCTIVE CELLS UTILIZING THE MOUSE CHIMERA ASSAY.*  O.G. Raabe,1
T. Straume,2 and L.M. Wiley 1 (1 Institute of Toxicology and Environmental
Health,
University of California, Davis, CA 95616; 2 Lawrence Livermore National
Laboratory,
Livermore, CA 94550) presented at the 1997 Health Physics Society Annual
Meeting, San
Antonio, Texas.

In previous studies the mouse chimera assay has shown sensitive responses
to irradiation by
both male and female reproductive germ cells. Chimeras are made with 4-cell
preimplantation
embryos and cultured for 30 hours to about 2 to 3 cell cycles. Cultured
chimeras are
dissociated to count the cells from each partner embryo and these cell
numbers are expressed
as a "proliferation ratio" (PR, number of cells from the affected embryo
divided by the total
number of cells in the chimera). A PR=0.5 occurs when both embryos exhibit
similar
proliferation rates, while a PR significantly less than 0.5 indicates a
proliferation disadvantage
for affected embryo cells. Significant decreases in PR have been observed
for paternal F0
irradiation with 137Cs   rays at particular times prior to F1 conception
for acute absorbed
doses from 0.01 Gy to 1 Gy. Similar results have been observed for maternal
F0 irradiation
for acute 137Cs   ray doses of about 0.1 Gy and for brief irradiation with
injected tritiated
thymidine for an absorbed dose of 0.2 Gy, indicating a cell nucleus target.
Recent studies
have found significant decreases in PR for F2 embryos obtained from F1
males that were
conceived 6 to 7 weeks after paternal F0 irradiation with an acute dose of
1 Gy of 137Cs  
rays showing heritable mutations. These results may be relevant to the
finding in Great
Britain of increased incidence of leukemia and non-Hodgkin's lymphoma in
children of
fathers employed at the Sellafield nuclear reprocessing plant. That no
increased leukemia in
offspring has been found for the Japanese atomic bomb survivors may be
explained by the
need to consider only irradiation during the sensitive part of
spermatogenesis. Germ cell
irradiation during critical periods prior to conception may require special
radiation safety
considerations.
*(This work was supported by USPHS NIH Grant R01 ES06516, L.M. Wiley, P.I.)

References:

Gardner RL, Snee MP, Hall AJ, Powell CA, Downes S and JD Terrell (1990)
Results of
case-control study of leukaemia and lymphoma among young people near
Sellafield nuclear
plant in West Cumbria. Brit Med J . 300:423.

Obasaju MF, Wiley LM, Oudiz DJ, Raabe OG and JW Overstreet (1989) A chimera
embryo
assay reveals a decrease in embryonic cellular proliferation induced by
sperm from
x-irradiated male mice.  Radiat Res, 118:246-256.

Warner  P, Wiley LM, Oudiz DJ, Overstreet JW and OG Raabe (1991)
Paternally-inherited
effects of gamma radiation on mouse preimplantation development detected by
the chimera
assay.  Radiat Res, 128:48-58.

Wiley LM, MF Obasaju (1986) Cell proliferation in mouse embryo aggregation
    
chimaeras. J Cell Biol, 103:88a.

Wiley LM, Yamami S and D Van Muyden (1986) Effect of potassium
concentration, type of
protein supplement and embryo density on mouse preimplantation development
in vitro. 
Fertil Steril, 45:111-119.

Wiley LM, Raabe OG, Khan R and T Straume (1994a) Radiosensitive target in
the early
mouse embryo exposed to very low doses of ionizing radiation.  Mutat Res,
309:83-92.

Wiley LM, Van Beek MEAB and OG Raabe (1994b) Embryonic effects transmitted
by male
mice irradiated with 512 MeV/amu 56Fe nuclei.  Radiat Res, 138:373-385.

Wiley, L.M., Baulsch, J.E., Raabe, O.G., Straume, T. (1997) Impaired Cell
Proliferation in
Mice That Persists Across at Least Two Generations after Paternal
Irradiation, Radiation
Research 148: 145-151.
*********************************************8
	*****************************************************
	Prof. Otto G. Raabe, Ph.D., CHP
	Institute of Toxicology & Environmental Health (ITEH)
	(Street Address: Bldg. 3792, Old Davis Road)
	University of California, Davis, CA 95616
	E-Mail: ograabe@ucdavis.edu
	Phone:(530) 752-7754, FAX:(530) 758-6140
	*****************************************************
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