Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation.
OBJECTIVE
To investigate the effects of preconception paternal irradiation (PPI) from injected 239Pu on the susceptibility to induction of lympho-haemopoietic malignancy by subsequent irradiation or exposure to a chemical carcinogen.


METHODS
The male CBA/H and DBA2 mouse was injected with 0, 128 or 256 Bqg(-1) 239Pu 12 weeks before mating with the normal CBA/H and C57B1 female respectively. CBA/H offspring were exposed to 3.3 Gy gamma-rays total body irradiation: BDF1 offspring were injected with 50 mg kg(-1) methyl nitrosourea (MNU). The offspring were assayed for changes in bone marrow progenitor cell numbers and chromosome aberrations and were followed up for subsequent induction of neoplasia.


RESULTS
While the untreated mouse showed a normal distribution for cellularity, spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), significant numbers of PPI offspring presented levels outside the normal range. There was a tendency for them also to show increased, dose-related, levels of chromosomal aberrations. Offspring treated with irradiation or MNU developed an increased incidence of lympho-haemopoietic malignancies.


CONCLUSIONS
These studies have shown that PPI results in offspring that are more susceptible to the induction of lymphohaemopoietic malignancy on encountering a secondary carcinogenic insult. This may be linked to inherited chromosomal instability and abnormal kinetics of haemopoiesis. The experiments indicate a potential mechanism by which an increased incidence of leukaemia may be linked to PPI.
Lord
B I
BI
CRC Sections of Experimental Haematology and Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Woolford
L B
LB
Wang
L
L
McDonald
D
D
Lorimore
S A
SA
Stones
V A
VA
Wright
E G
EG
Scott
D
D
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000235:genetics; D003114:Colony-Forming Units Assay; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D007942:Leukemia, Experimental / Q000235:genetics; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000494:pharmacology; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D018812:Paternal Exposure / Q000009:adverse effects*; D011005:Plutonium / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013154:Spleen / Q000473:pathology; D014916:Whole-Body Irradiation
D002273:Carcinogens; D009153:Mutagens; D011005:Plutonium; D008770:Methylnitrosourea