Infiltrating angiolipoma of skeletal muscle. Transplacental induction in nonhuman primates by N-nitrosoethylurea.
BACKGROUND
In humans, relatively little is known on the association of prenatal exposure to cancer-causing agents and the development of specific tumors later in life as a consequence. Therefore, the effects on the offspring of carcinogen exposure during gestation and the development of tumors later in life were studied in nonhuman primates.


METHODS
Pregnancy was confirmed in Erythrocebus patas (patas) and Macaca mulatta (rhesus) by palpation at 27 to 40 days of gestation. Pregnant animals were treated once weekly intravenously from that time with N-nitrosoethylurea according to different dosing regimens for 6 to 19 weeks with 0.05 to 0.2 mmol/kg/injection.


RESULTS
A common lesion developing in only the offspring of mothers treated early in pregnancy was identical with the human condition referred to as intramuscular angioma, hemangioma, or infiltrating angiolipoma of skeletal muscle. In the rhesus, one of 7 animals, and in the patas, 18 of 78 monkeys developed these processes (10 to 40% per group). The lesions typically arose within, infiltrated and displaced skeletal muscle. They occurred most commonly in the lower extremities, followed by the upper extremities and the head; they recurred in three cases of incomplete resection but did not metastasize. The tumors were seen mainly in young adults of both sexes (latency range: 4 to 76 months) and consisted of vessels of variable caliber, and to varying degrees, mature adipose and connective tissue, undifferentiated mesenchymal cells, and lymphoid cell aggregates. Ultrastructurally, the endothelium possessed numerous Weibel-Palade bodies and showed strong immunoreactivity for von Willebrand factor by immunohistochemistry and immunoelectron microscopy.


CONCLUSIONS
The present investigation suggests a classification of these lesions as infiltrating angiolipoma of skeletal muscle originating from a pluripotent mesenchymal stem cell, caused by exposure to carcinogens during early pregnancy. The great clinical and morphologic similarity of this condition with that observed in humans suggests that it may likewise be caused by exposure to an agent during pregnancy.
Rehm
S
S
Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
Palmer
A E
AE
Harbaugh
S W
SW
Rice
J M
JM
D000818:Animals; D004901:Erythrocebus patas; D005038:Ethylnitrosourea; D005260:Female; D006391:Hemangioma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008067:Lipoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D005038:Ethylnitrosourea