Horstman M G, Meadows G G, Yost G S
Cancer Res. 1987 Mar 15;47(6):1547-50.
Procarbazine causes dose-dependent decreases in sperm count after a single i.p. injection in (C57BL/6 X DBA/2)F1 male mice. Two antioxidants, N-acetylcysteine and sodium ascorbate, administered with equimolar doses of procarbazine decreased the spermatotoxicity of procarbazine. At the highest doses of procarbazine (400 mg/kg) that caused a 56% decrease in sperm count, equimolar doses of N-acetylcysteine coadministered with procarbazine caused only a 17% decrease in sperm count, and equimolar doses of ascorbate coadministered with procarbazine caused only a 13% decrease in sperm count. Thus, protection against the spermatotoxic effects of procarbazine was demonstrated with either antioxidant. The effect of the antioxidants on the chemotherapeutic efficacy of procarbazine against murine L1210 leukemia was also assessed. Procarbazine at the highest dose (600 mg/kg) increased mean survival time of mice inoculated i.p. with 1 X 10(5) L1210 leukemia cells by 31%. Simultaneous administration of equimolar doses of either N-acetylcysteine or ascorbate given with procarbazine caused no change in the increased mean survival time of tumor-bearing mice. These results indicate a decrease in the toxicity of procarbazine when coadministered with antioxidants, via decreased spermatotoxicity without changing anticancer efficacy. The results also indicate that different mechanisms are involved in the spermatotoxicity and anticancer activity of procarbazine.
在（C57BL/6×DBA/2）F1雄性小鼠中，单次腹腔注射丙卡巴肼会导致精子数量呈剂量依赖性减少。两种抗氧化剂N-乙酰半胱氨酸和抗坏血酸钠，与等摩尔剂量的丙卡巴肼同时给药，可降低丙卡巴肼的精子毒性。在导致精子数量减少56%的最高丙卡巴肼剂量（400mg/kg）下，与丙卡巴肼同时给药的等摩尔剂量N-乙酰半胱氨酸仅导致精子数量减少17%，与丙卡巴肼同时给药的等摩尔剂量抗坏血酸仅导致精子数量减少13%。因此，两种抗氧化剂均显示出对丙卡巴肼精子毒性作用的保护作用。还评估了抗氧化剂对丙卡巴肼抗小鼠L1210白血病化疗疗效的影响。最高剂量（600mg/kg）的丙卡巴肼可使腹腔接种1×10⁵个L1210白血病细胞的小鼠平均存活时间延长31%。与丙卡巴肼同时给予等摩尔剂量的N-乙酰半胱氨酸或抗坏血酸，对荷瘤小鼠延长的平均存活时间没有影响。这些结果表明，丙卡巴肼与抗氧化剂同时给药时，通过降低精子毒性而不改变抗癌疗效，其毒性降低。结果还表明，丙卡巴肼的精子毒性和抗癌活性涉及不同的机制。
