Acrylamide exposure induces a delayed unscheduled dna synthesis in germ cells of male mice that is correlated with the temporal pattern of adduct formation in testis DNA

Abstract

A study of meiotic and postmeiotic germ-cell-stage sensitivity of male mice to induction of unscheduled DNA synthesis (UDS) by acrylamide showed that DNA repair could be detected in early spermatocytes (after the last scheduled DNA synthesis) through about mid-spermatid stages. No DNA repair could be detected in later stages. The maximum UDS response was observed 6 hr after i.p. exposure and was about 5 times greater than the response measured immediately after treatment. This is the longest delay between chemical treatment and maximum UDS response yet observed in mouse germ cells. There was a linear relationship between the UDS response and acrylamide exposure from 7.8 to 125 mg/kg. By using 14C-labeled acrylamide it was determined that the temporal pattern of adduct formation in testes DNA paralleled that of the UDS response, with maximum binding occurring 4 to 6 hr after exposure. In contrast, the temporal pattern of adduct formation in liver DNA showed maximum binding within 1 to 2 hr after exposure and was an order of magnitude greater than that found for the testis DNA.

Induction of micronuclei in bone marrow and sperm head abnormalities after combined exposure of mice to low doses of X-rays and acrylamide

“…A lower frequency of pregnant females obtained after exposure of spermatozoa to AA and X-rays + AA [14] can be compared to a higher frequency of sperm head abnormalities, because malformed spermatozoa are not able to fertilize. Also, the results of other AA studies suggest that the late spermatids and spermatozoa are the most susceptible to damage [13,15,17,[44][45][46] . In previous studies, a significant increase in micronucleus frequency in bone marrow was observed 24 h after treatment with 50-100 mg/kg bw of AA [4,6,7].…”

Scientific Opinion on acrylamide in food

“…injections of 0-125 mg AA/kg b.w. (Sega et al, 1990). The testes were injected with tritiated thymidine either at the time of AA treatment or at later times, up to 48 hours following AA exposure.…”

“…The DNA alkylation levels in the testes were about 10-fold lower than in the liver. Based on these results, the authors concluded that AA or, more likely a metabolite, is able to interact with DNA and elicit a UDS response in early spermatocytes through mid-spermatid stages (Sega et al, 1990).…”

“…Sega et al (1990) found that 7.8 and 125 mg AA/kg b.w. applied to male mice resulted in DNA binding and increased UDS in testis or early spermatocytes, respectively.…”

Comparison of Germ Cell Mutagenicity in Male CYP2E1-Null and Wild-Type Mice Treated with Acrylamide: Evidence Supporting a Glycidamide-Mediated Effect

“…Subsequent studies of genetic effects, DNA adduct formation, and unscheduled DNA synthesis in spermiogenic cells after acrylamide exposure led to the proposal of a glycidamidemediated mutagenic pathway via DNA or protamine alkylation [24][25][26]. Consistent with this hypothesis, glycidamide has been shown to induce dominant lethal mutations in male mice, with the most sensitive stages being spermatozoa of the testis and epididymis [27]; these are the same stages that show the highest sensitivity to dominant lethal induction by acrylamide.…”