Working P K, Bentley K S, Hurtt M E, Mohr K L
Department of Genetic Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Mutagenesis. 1987 May;2(3):215-20. doi: 10.1093/mutage/2.3.215.
Acrylonitrile (ACN) and acrylamide (AA), structurally similar vinyl monomers, are both animal carcinogens. ACN is weakly mutagenic in bacteria and induces sister-chromatid exchange, unscheduled DNA synthesis and cell transformation in cells in culture. AA induces chromosomal aberrations in bone marrow, blood and germ cells in vivo, and dominant lethal mutations in the germ cells of male mice and rats. In the current study, the ability of AA and ACN to induce dominant lethal mutations in the germ cells of male Fischer 344 rats was compared. Three groups of 50 males were gavaged daily for 5 days with ACN (60 mg/kg in normal saline), AA (30 mg/kg in normal saline) or vehicle only; an additional group of 20 males received a single i.p. injection of 0.2 mg/kg triethylenemelamine (TEM) on the afternoon of day 5. Starting 1 day after exposure, each male was bred to one female per week for 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and control groups). Mating rates were reduced only during week 1 in the TEM-treated group; pregnancy rates were reduced only during week 2 in the AA-exposed group and week 4 in the TEM-treated group. Females were necropsied 13 days after the end of the appropriate mating week and the amount of pre- and post-implantation loss calculated. ACN treatment of male rats induced no increases in either pre- or post-implantation loss in females in any of the 10 weeks post-exposure examined.(ABSTRACT TRUNCATED AT 250 WORDS)
丙烯腈(ACN)和丙烯酰胺(AA)是结构相似的乙烯基单体,二者均为动物致癌物。ACN在细菌中具有弱致突变性,并可在培养细胞中诱导姐妹染色单体交换、非程序性DNA合成及细胞转化。AA可在体内诱导骨髓、血液和生殖细胞中的染色体畸变,以及雄性小鼠和大鼠生殖细胞中的显性致死突变。在本研究中,比较了AA和ACN诱导雄性Fischer 344大鼠生殖细胞中显性致死突变的能力。将三组各50只雄性大鼠每天经口灌胃5天,分别给予ACN(60 mg/kg溶于生理盐水)、AA(30 mg/kg溶于生理盐水)或仅给予赋形剂;另一组20只雄性大鼠在第5天下午单次腹腔注射0.2 mg/kg三亚乙基三聚氰胺(TEM)。从暴露后1天开始,每组雄性大鼠每周与一只雌性大鼠交配,持续4周(TEM暴露组)或10周(ACN、AA和对照组)。仅在TEM处理组的第1周交配率降低;仅在AA暴露组的第2周和TEM处理组的第4周妊娠率降低。在适当交配周结束后13天对雌性大鼠进行尸检,并计算植入前和植入后的损失量。在暴露后的10周内,对雄性大鼠进行ACN处理后未导致雌性大鼠植入前或植入后损失量增加(摘要截断于250字)。